Structural and functional aspects of the myosin essential light chain in cardiac muscle contraction.

The myosin essential light chain (ELC) is a structural component of the actomyosin cross-bridge, but its function is poorly understood, especially the role of the cardiac specific N-terminal extension in modulating actomyosin interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine to glycine) mutation in the cardiac ELC known to cause familial hypertrophic cardiomyopathy (FHC). The function of the ELC N-terminal extension was investigated with the Tg-Δ43 mouse model, whose myocardium expresses a truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in rigor revealed a decreased interfilament spacing (≈ 1.5 nm) and no alterations in cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in I(1,1)/I(1,0), indicating a shift of cross-bridge mass from the thick filament backbone toward the thin filaments. Mechanical studies demonstrated increased stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-Δ43. The equilibrium constant for the cross-bridge force generation step was smallest in Tg-Δ43. These results support an important role for the N-terminal ELC extension in prepositioning the cross-bridge for optimal force production. Subtle changes in the ELC sequence were sufficient to alter cross-bridge properties and lead to pathological phenotypes.

[Exercise tolerance and fatigue in women survivors of non-metastatic breast cancer]. / Tolerancia al ejercicio y fatiga en mujeres sobrevivientes de cáncer de mama no metastásico.

BACKGROUND: Breast cancer is the most common type of cancer worldwide, and the leading cause of disability and death in young women in Latin America. One of the most common symptoms in this population is fatigue, reported by 70 to 100% of survivors. OBJECTIVE: To describe the relationship between exercise tolerance and fatigue in women survivors of non-metastatic breast cancer. MATERIALS AND METHODS: Cross-sectional descriptive study in 40 women between 18 and 65 years of age, from a database pertaining to a highly complex healthcare institution in the city of Cali, Colombia. The relationship between fatigue and exercise tolerance was identified using the "Functional Assessment of Cancer Therapy FACT-F" questionnaire and the 6-minute walk test (TC6M). RESULTS: 37.5% of the participants presented fatigue related to breast cancer; 33% of women presented dyspnea at the end of the TC6M, 37.5% reported having lower limb fatigue (modified Borg) and 42.5% did not reach 80% of the predicted distance in the TC6M. CONCLUSION: A positive correlation (p 0.000) was found between fatigue and exercise tolerance in women survivors of non-metastatic breast cancer.

BACKGROUND: El cáncer de mama es el más frecuente a nivel mundial y la principal causa de discapacidad y muerte en mujeres jóvenes en América Latina. Uno de los síntomas más comunes en esta población es la fatiga, reportada entre el 70 y 100% de mujeres sobrevivientes. OBJETIVO: Describir la relación entre tolerancia al ejercicio y la fatiga, en mujeres sobrevivientes de cáncer de mama no metastásico. MATERIALES Y MÉTODOS: Estudio descriptivo transversal en 40 mujeres entre 18 y 65 años, a partir de una base de datos de una institución de alta complejidad en la ciudad de Cali, Colombia. Se identificó la relación entre fatiga y tolerancia al ejercicio con el cuestionario " The Functional Assessment of Cancer Therapy FACT-F" y el test de caminata de los 6 minutos (TC6M). RESULTADOS: El 37,5% de las participantes presentaron fatiga relacionada con cáncer de mama; 33% de las mujeres, disnea al final del TC6M; 37,5%, fatiga en miembros inferiores (Borg modificada), y el 42,5% no alcanzó el 80% de la distancia predicha del TC6M. CONCLUSIÓN: Se encontró una correlación positiva (p 0,000) entre fatiga y tolerancia al ejercicio en mujeres sobrevivientes de cáncer de mama no metastásico.

[Knowledge, attitudes, practices and education among students in a faculty of health]. / Conocimientos, actitudes, prácticas y educación sobre tuberculosis en estudiantes de una facultad de salud.

Objective To determine tuberculosis (TB) knowledge, attitudes, practices, education and Tuberculin Skin Test (TST) positivity among Colombian health professions students in their last year of study. Methods A cross-sectional study was conducted using a self-reported questionnaire about TB knowledge, attitudes, practices and education with 193 students of medicine, nursing, dentistry, physical therapy, speech and language therapy, occupational therapy, clinical laboratory studies and emergency care. A TST was performed on 153 of the students. Results Although most of survey respondents perceived the TB education they received to be "sufficient", the results regarding their knowledge of TB do not support such perceptions: 35.2% of participants did not identify TB risk factors, 33.7 % of participants identified Colombian TB incidence, and only 1.6 % identified appropriate initial treatment for TB. In regards to practices, 50 % of respondents admitted that they would take care of a patient without a high efficiency mask. The TST was positive in 35 % of participants. Conclusions Our results show that there are opportunities to improve TB education in this health faculty, there is also a need to improve safety practices in the facilities where students work in order to reduce their risk of conversion.

Tolerancia al ejercicio y fatiga en mujeres sobrevivientes de cáncer de mama no metastásico / Exercise tolerance and fatigue in women survivors of non-metastatic breast cancer

RESUMEN El cáncer de mama es el más frecuente a nivel mundial y la principal causa de discapacidad y muerte en mujeres jóvenes en América Latina. Uno de los síntomas más comunes en esta población es la fatiga, reportada entre el 70 y 100% de mujeres sobrevivientes. Objetivo Describir la relación entre tolerancia al ejercicio y la fatiga, en mujeres sobrevivientes de cáncer de mama no metastásico. Materiales y Métodos Estudio descriptivo transversal en 40 mujeres entre 18 y 65 años, a partir de una base de datos de una institución de alta complejidad en la ciudad de Cali, Colombia. Se identificó la relación entre fatiga y tolerancia al ejercicio con el cuestionario " The Functional Assessment of Cancer Therapy FACT-F" y el test de caminata de los 6 minutos (TC6M). Resultados El 37,5% de las participantes presentaron fatiga relacionada con cáncer de mama; 33% de las mujeres, disnea al final del TC6M; 37,5%, fatiga en miembros inferiores (Borg modificada), y el 42,5% no alcanzó el 80% de la distancia predicha del TC6M. Conclusión Se encontró una correlación positiva (p 0,000) entre fatiga y tolerancia al ejercicio en mujeres sobrevivientes de cáncer de mama no metastásico.(AU)

ABSTRACT Breast cancer is the most common type of cancer worldwide, and the leading cause of disability and death in young women in Latin America. One of the most common symptoms in this population is fatigue, reported by 70 to 100% of survivors. Objective To describe the relationship between exercise tolerance and fatigue in women survivors of non-metastatic breast cancer. Materials and Methods Cross-sectional descriptive study in 40 women between 18 and 65 years of age, from a database pertaining to a highly complex healthcare institution in the city of Cali, Colombia. The relationship between fatigue and exercise tolerance was identified using the "Functional Assessment of Cancer Therapy FACT-F" questionnaire and the 6-minute walk test (TC6M). Results 37.5% of the participants presented fatigue related to breast cancer; 33% of women presented dyspnea at the end of the TC6M, 37.5% reported having lower limb fatigue (modified Borg) and 42.5% did not reach 80% of the predicted distance in the TC6M. Conclusion A positive correlation (p 0.000) was found between fatigue and exercise tolerance in women survivors of non-metastatic breast cancer.(AU)

Conocimientos, actitudes, prácticas y educación sobre tuberculosis en estudiantes de una facultad de salud / Knowledge, attitudes, practices and education among students in a faculty of health

Objetivo Determinar los conocimientos, actitudes, prácticas y educación relacionados con Tuberculosis, así como la reactividad a la prueba cutánea de tuberculina de estudiantes de último año de una facultad de salud. Método Se realizó un estudio transversal utilizando un cuestionario diseñado y validado por los investigadores para indagar los conocimientos, actitudes, prácticas y educación relacionados con tuberculosis en 193 estudiantes de último año de los programas de medicina, enfermería, odontología, fisioterapia, fonoaudiología, terapia ocupacional, laboratorio clínico y atención pre-hospitalaria. Se realizó la prueba cutánea de tuberculina en 153 de los encuestados. Resultados Aunque la mayoría de los encuestados calificaron como suficiente la educación recibida sobre tuberculosis, los resultados sobre conocimientos no apoyan esta percepción: 35,2 % de los estudiantes no identificaron apropiadamente los factores de riesgo para tuberculosis nosocomial, solo 33,7 % conocían la incidencia de tuberculosis en el país y un 1,6 % de los encuestados identificó apropiadamente el tratamiento de primera línea para tuberculosis. En cuanto a las prácticas, un 50 % de los encuestados admitió que realizaría la atención de un paciente con tuberculosis sin máscara de alta eficiencia. De acuerdo a la prueba cutánea de tuberculina, 35 % de los estudiantes tenía tuberculosis latente. Conclusiones Los resultados indican que existen oportunidades para mejorar la educación que reciben los estudiantes de esta facultad con respecto a la tuberculosis, además es necesario mejorar las medidas de protección en los contextos en que se llevan a cabo las prácticas de los estudiantes para reducir el riesgo de conversión.(AU)

Objective To determine tuberculosis (TB) knowledge, attitudes, practices, education and Tuberculin Skin Test (TST) positivity among Colombian health professions students in their last year of study. Methods A cross-sectional study was conducted using a self-reported questionnaire about TB knowledge, attitudes, practices and education with 193 students of medicine, nursing, dentistry, physical therapy, speech and language therapy, occupational therapy, clinical laboratory studies and emergency care. A TST was performed on 153 of the students. Results Although most of survey respondents perceived the TB education they received to be "sufficient", the results regarding their knowledge of TB do not support such perceptions: 35.2% of participants did not identify TB risk factors, 33.7 % of participants identified Colombian TB incidence, and only 1.6 % identified appropriate initial treatment for TB. In regards to practices, 50 % of respondents admitted that they would take care of a patient without a high efficiency mask. The TST was positive in 35 % of participants. Conclusions Our results show that there are opportunities to improve TB education in this health faculty, there is also a need to improve safety practices in the facilities where students work in order to reduce their risk of conversion.(AU)

The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction.

To study the regulation of cardiac muscle contraction by the myosin essential light chain (ELC) and the physiological significance of its N-terminal extension, we generated transgenic (Tg) mice by partially replacing the endogenous mouse ventricular ELC with either the human ventricular ELC wild type (Tg-WT) or its 43-amino-acid N-terminal truncation mutant (Tg-Delta43) in the murine hearts. The mutant protein is similar in sequence to the short ELC variant present in skeletal muscle, and the ELC protein distribution in Tg-Delta43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Delta43 mice demonstrate reduced force per cross-sectional area of muscle, which is likely caused by a reduced number of force-generating myosin cross-bridges and/or by decreased force per cross-bridge. As the mice grow older, the contractile force per cross-sectional area further decreases in Tg-Delta43 mice and the mutant hearts develop a phenotype of nonpathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Delta43 mice also exhibits reduced myosin content. Our results suggest that the role of the N-terminal ELC extension is to maintain the integrity of myosin and to modulate force generation by decreasing myosin neck region compliance and promoting strong cross-bridge formation and/or by enhancing myosin attachment to actin.

Myosin essential light chain in health and disease.

The essential light chain of myosin (ELC) is known to be important for structural stability of the alpha-helical lever arm domain of the myosin head, but its function in striated muscle contraction is poorly understood. Two ELC isoforms are expressed in fast skeletal muscle, a long isoform and its NH(2)-terminal approximately 40 amino acid shorter counterpart, whereas only the long ELC is observed in the heart. Biochemical and structural studies revealed that the NH(2)-terminus of the long ELC can make direct contacts with actin, but the effects of the ELC on the affinity of myosin for actin, ATPase, force, and the kinetics of force generating myosin cross-bridges are inconclusive. Myosin containing the long ELC has been shown to have slower cross-bridge kinetics than myosin with the short isoform. A difference was also reported among myosins with long isoforms. Increased shortening velocity was observed in atrial compared with ventricular muscle fibers. The common findings suggest that ELC provides the fine tuning of the myosin motor function, which is regulated in an isoform and tissue-dependent manner. The functional importance of the ELC is further implicated by the discovery of ELC mutations associated with Familial Hypertrophic Cardiomyopathy. The pathological phenotypes vary in severity, but more notably, almost all ELC mutations result in sudden cardiac death at a young age. This review summarizes the functional roles of striated muscle ELC in normal healthy muscle and in disease. Transgenic animal models and phenotypic characterization of ELC-mediated remodeling of the heart are also discussed.

F110I and R278C troponin T mutations that cause familial hypertrophic cardiomyopathy affect muscle contraction in transgenic mice and reconstituted human cardiac fibers.

We have studied the physiological effects of the troponin T (TnT) F110I and R278C mutations associated with familial hypertrophic cardiomyopathy (FHC) in humans. Three to four-month-old transgenic (Tg) mice expressing F110I-TnT and R278C-TnT did not develop significant hypertrophy or ventricular fibrosis even after chronic exercise challenge. The F110I mutation impaired acute exercise tolerance, whereas R278C did not. Skinned papillary muscle fibers from transgenic mice expressing F110I-TnT demonstrated increased Ca(2+) sensitivity of force and ATPase activity, and likewise an increased Ca(2+) sensitivity of force was observed in F110I-TnT-reconstituted human cardiac muscle preparations. In contrast, no changes in force or the ATPase-pCa dependencies were observed in transgenic R278C fibers or in human fibers reconstituted with the R278C-TnT mutant. The maximal level of force development was dramatically decreased in both transgenic mice. However, the maximal ATPase was not different (R278C-TnT) or only slightly less (F110I-TnT) than that of non-Tg and WT-Tg littermates. Consequently, their ratios of ATPase/force (energy cost) at all Ca(2+) concentrations were dramatically higher compared with non-Tg and WT-Tg fibers. This increase in energy cost most likely results from a decrease in force per myosin cross-bridge, because forcing all cross-bridges into the force generating state by substitution of MgADP for MgATP in maximum contracting solutions resulted in the same increase in maximal force (15%) in all transgenic and non-transgenic preparations. The combination of increased Ca(2+) sensitivity and energy cost in the F110I hearts may be responsible for the greater severity of this phenotype compared with the R278C mutation.

Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3.

Coronary artery disease leads to injury and loss of myocardial tissue by deprivation of blood flow (ischemia) and is a major underlying cause of heart failure. Prolonged ischemia causes necrosis and apoptosis of cardiac myocytes and vascular cells; however, the mechanisms of ischemia-mediated cell death are poorly understood. Ischemia is associated with both hypoxia and acidosis due to increased glycolysis and lactic acid production. We recently reported that hypoxia does not induce cardiac myocyte apoptosis in the absence of acidosis. We now report that hypoxia-acidosis-associated cell death is mediated by BNIP3, a member of the Bcl-2 family of apoptosis-regulating proteins. Chronic hypoxia induced the expression and accumulation of BNIP3 mRNA and protein in cardiac myocytes, but acidosis was required to activate the death pathway. Acidosis stabilized BNIP3 protein and increased the association with mitochondria. Cell death by hypoxia-acidosis was blocked by pretreatment with antisense BNIP3 oligonucleotides. The pathway included extensive DNA fragmentation and opening of the mitochondrial permeability transition pore, but no apparent caspase activation. Overexpression of wild-type BNIP3, but not a translocation-defective mutant, activated cardiac myocyte death only when the myocytes were acidic. This pathway may figure significantly in muscle loss during myocardial ischemia.

Valoración del programa "enfermería de urgencia", licenciatura en enfermería / Assessment of the Emergency Nursing Program. Bachelor of Science in Nursing

El diseño curricular en las profesiones de ciencias de la salud constituye en la actualidad uno de los campos teóricos y prácticos que concita mayores debates. Baste decir que la pretensión que subyace es la de diseñar planes de estudio que conduzcan a la formación de un egresado congruente con las expectativas de la sociedad en función de sus necesidades de salud, de modo que el futuro profesional adquiera los conocimientos, habilidades y valores que lo capaciten para desempeñar plenamente las funciones que de él se esperan una vez graduado, por lo que realizamos una valoración del Programa de Enfermería de Urgencias, para lo que tuvimos en cuenta todas las categorías de la didáctica: problema, objetivo, contenido, métodos, medios y evaluación. Considerando que el programa tributa a la formación del egresado a que se aspira formar. Con este trabajo pretendemos realizar una valoración crítica del programa de esta asignatura.

The Curricular Design in the Medical Science professions is one of the most debated theoretic and practical field nowadays. The aim is to design study plans which lead to the formation of a graduate consistent with the expectations of society according to its health requirements ,so we made an evaluation of the Nursing Emergency Program bearing in mind all the following didactic categories: problem, objective , methods , aids and valuation. The program is considered tributary to the formation of the graduate.

Comportamiento de la tuberculosis pulmonar / Behavior of pulmonary tuberculosis

En los últimos 20 años la tuberculosis pulmonar tuvo un comportamiento favorable, con tendencia a la disminución en todo el país. Se realizó un estudio comparativo en el área del policlínico ôTurcios Limaö en los años 1998-1999, pues a pesar de existir una tendencia favorable a la disminución en todo el país, están presentes diversos factores como el surgimiento de cepas multirresistentes a las drogas en uso y escasez de recursos. Como fuente de datos empleamos el Registro de Notificaciones de Casos del Departamento de Estadística; se utilizó como muestra 19 pacientes de un total de 22 y recogimos las siguientes variables: edad, sexo, género de vida, hábitos y condiciones de vida, así como el grado de conocimiento hacia esta enfermedad. Las cifras que resultaron del procesamiento de los datos arrojaron que en el año 1998 hubo incremento considerable, con mayor incidencia en el adulto mayor de 60 años, además de factores predisponentes como: mala alimentación, hábito de fumar y falta de higiene general, que se vieron en la mayoría de los casos estudiados. Para lo anteriormente expuesto debemos mejorar la cantidad y calidad en la búsqueda de nuevas fuentes de identificación y mantener un tratamiento eficaz con pacientes y contactos. Llegamos a la conclusión que todavía existe desconocimiento por parte de la población de las medidas de prevención y control y la necesidad de seguir trabajando en la atención primaria para disminuir la incidencia de esta enfermedad(AU)

During the last 20 years pulmonary tuberculosis has had a favorable behavior with a trend to decrease all over the country. A comparative study was conducted in "Turcios Lima" health area from 1998 to 1999, since in spite of this trend there are diverse factors that should be analyzed as the appearance of strains multiresistant to drugs in use and scarcity of resources. We used the Registration of Case Reports from the Statistics Department as a source of data. 19 of the 22 patients were included in the sample and the following variables were considered: age, sex, way of life, habits and living conditions and the degree of knowledge about this disease. The figures resulting from the processing of data showed that in 1998 there was a significant increase with a higher incidence in the adult over 60. Predisposing factors, such as poor nourishment, smoking habit and lack of general hygiene were observed in most of the studied cases. To contribute to solve this situation, we have to improve the quality and quantity in the search for new sources of identification and to maintian an efficient treatment with patients and contacts. We concluded that more information should be given to the population about the measures of prevention and control and that it is necessary to keep on working at the primary health care level to reduce the incidence of this disease(AU)