[Numeric alterations in the dys gene and their association with clinical features]. / Detección de alteraciones numéricas en el gen dys y su asociación con rasgos clínicos.

The Duchenne/Becker muscular dystrophy is a hereditary miopathy with a recessive sex-linked pattern. The related gene is called DYS and the coded protein plays a crucial role in the anchorage between the cytoskeleton and the cellular membrane in muscle cells. Different clinical manifestations are observed depending on the impact of the genetic alteration on the protein. The global register of mutations reveals an enhanced frequency for deletions/duplications of one or more exons affecting the DYS gene. In the present work, numeric alterations have been studied in the 79 exons of the DYS gene. The study has been performed on 59 individuals, including 31 independent cases and 28 cases with a familial link. The applied methodology was Multiplex Ligation Dependent Probe Amplification (MLPA). In the 31 independent cases clinical data were established: i.e. the clinical score, the Raven test percentiles, and the creatininphosphokinase (CPK) blood values. Our results reveal a 61.3% frequency of numeric alterations affecting the DYS gene in our population, provoking all of them a reading frame shift. The rate for de novo mutations was identified as 35.2%. Alterations involving a specific region of one exon were observed with high frequency, affecting a specific region. A significant association was found between numeric alterations and a low percentile for the Raven test. These data contribute to the local knowledge of genetic alterations and their phenotypic impact for the Duchenne/Becker disease.

Developing performance-based medical school assessment programs in resource-limited environments.

While the use of performance-based assessments in medical schools is widespread, there are unique issues associated with developing and establishing simulated clinical examinations when resources are limited. The faculty at the National University of Cuyo (NUC) in Mendoza, Argentina, has successfully implemented an OSCE as part of the medical school graduation requirements. This paper provides an overview of the issues faced by NUC faculty in setting up a standardized patient (SP)-based assessment with only limited resources, and contrasts their experiences with those of other groups, including certification and licensure bodies who have implemented similar types of assessments. Despite their novelty and a lack of technological, staffing, and budgetary resources, with adequate planning, an emphasis on faculty involvement, quality case development, local SP recruitment and training activities, educational programs focused on assessment, and flexibility in creating a physical space to conduct the exam, an effective program for assessing the clinical skills of medical students can be realized.

Mutations of ARX are associated with striking pleiotropy and consistent genotype-phenotype correlation.

We recently identified mutations of ARX in nine genotypic males with X-linked lissencephaly with abnormal genitalia (XLAG), and in several female relatives with isolated agenesis of the corpus callosum (ACC). We now report 13 novel and two recurrent mutations of ARX, and one nucleotide change of uncertain significance in 20 genotypic males from 16 families. Most had XLAG, but two had hydranencephaly and abnormal genitalia, and three males from one family had Proud syndrome or ACC with abnormal genitalia. We obtained detailed clinical information on all 29 affected males, including the nine previously reported subjects. Premature termination mutations consisting of large deletions, frameshifts, nonsense mutations, and splice site mutations in exons 1 to 4 caused XLAG or hydranencephaly with abnormal genitalia. Nonconservative missense mutations within the homeobox caused less severe XLAG, while conservative substitution in the homeodomain caused Proud syndrome. A nonconservative missense mutation near the C-terminal aristaless domain caused unusually severe XLAG with microcephaly and mild cerebellar hypoplasia. In addition, several less severe phenotypes without malformations have been reported, including mental retardation with cryptogenic infantile spasms (West syndrome), other seizure types, dystonia or autism, and nonsyndromic mental retardation. The ARX mutations associated with these phenotypes have included polyalanine expansions or duplications, missense mutations, and one deletion of exon 5. Together, the group of phenotypes associated with ARX mutations demonstrates remarkable pleiotropy, but also comprises a nearly continuous series of developmental disorders that begins with hydranencephaly, lissencephaly, and agenesis of the corpus callosum, and ends with a series of overlapping syndromes with apparently normal brain structure.

Detección de alteraciones numéricas en el gen dys y su asociación con rasgos clínicos / Numeric alterations in the dys gene and their association with clinical features

La distrofia muscular de Duchenne/Becker (DMD/B) es una miopatía hereditaria grave y progresiva. Se relaciona con alteraciones en el gen DYS, ubicado en el cromosoma X, que codifica para la proteína distrofina. Distintas manifestaciones pueden observarse según el impacto de la alteración genética sobre la proteína. Los registros internacionales de mutaciones refieren una elevada frecuencia (65-70%) de deleciones/duplicaciones de uno o más exones del gen DYS. En este trabajo presentamos el estudio de alteraciones numéricas en los 79 exones del gen DYS. El estudio fue realizado en 59 individuos pertenecientes a 31 familias no relacionadas. La metodología utilizada fue Multiplex Ligation Dependent Probe Amplification (MLPA). En los 31 casos independientes se estableció además el score clínico, se realizó el test de Raven y se determinaron los valores de creatininfosfoquinasa (CPK) en sangre. Nuestros datos revelan una frecuencia de alteraciones numéricas en el gen DYS del 61.3%, provocando un corrimiento del marco de lectura en el 100% de los casos. Se observó una región con mayor tendencia a presentar alteraciones que involucran un solo exón. La tasa de mutación de novo identificada fue del 35.2%. Se halló, a su vez, una asociación significativa entre afectados con alteraciones numéricas y valores del test de Raven de bajo rendimiento. Estos resultados aportan datos a los conocimientos regionales sobre las alteraciones genéticas y su impacto fenotípico en la enfermedad de Duchenne/Becker.

The Duchen ne/Becker muscular dystrophy is a hereditary miopathy with a recessive sex-linked pattern. The related gene is called DYS and the coded protein plays a crucial role in the anchorage between the cytoskeleton and the cellular membrane in muscle cells. Different clinical manifestations are observed depending on the impact of the genetic alteration on the protein. The global register of mutations reveals an enhanced frequency for deletions/duplications of one or more exons affecting the DYS gene. In the present work, numeric alterations have been studied in the 79 exons of the DYS gene. The study has been performed on 59 individuals, including 31 independent cases and 28 cases with a familial link. The applied methodology was Multiplex Ligation Dependent Probe Amplification (MLPA). In the 31 independent cases clinical data were established: i.e. the clinical score, the Raven test percentiles, and the creatininphosphokinase (CPK) blood values. Our results reveal a 61.3% frequency of numeric alterations affecting the DYS gene in our population, provoking all of them a reading frame shift. The rate for de novo mutations was identified as 35.2%. Alterations involving a specific region of one exon were observed with high frequency, affecting a specific region. A significant association was found between numeric alterations and a low percentile for the Raven test. These data contribute to the local knowledge of genetic alterations and their phenotypic impact for the Duchenne/Becker disease.

Accreditation of undergraduate medical training programs: practices in nine developing countries as compared with the United States.

CONTEXT AND OBJECTIVES: Undergraduate medical training program accreditation is practiced in many countries, but information from developing countries is sparse. We compared medical training program accreditation systems in nine developing countries, and compared these with accreditation practices in the United States of America (USA). METHODS: Medical program accreditation practices in nine developing countries were systematically analyzed using all available published documents. Findings were compared to USA accreditation practices. FINDINGS: Accreditation systems with explicitly defined criteria, standards and procedures exist in all nine countries studied: Argentina, India, Kenya, Malaysia, Mongolia, Nigeria, Pakistan, Philippines and South Africa. Introduction of accreditation processes is relatively recent, starting in 1957 in India to 2001 in Malaysia. Accrediting agencies were set up in these countries predominantly by their respective governments as a result of legislation and acts of Parliament, involving Ministries of Education and Health. As in the USA, accreditation: (1) serves as a quality assurance mechanism promoting professional and public confidence in the quality of medical education, (2) assists medical schools in attaining desired standards, and (3) ensures that graduates' performance complies with national norms. All nine countries follow similar accreditation procedures. Where mandatory accreditation is practiced, non-compliant institutions may be placed on probation, student enrollment suspended or accreditation withdrawn. CONCLUSION: Accreditation systems in several developing countries are similar to those in the developed world. Data suggest the trend towards instituting quality assurance mechanisms in medical education is spreading to some developing countries, although generalization to other areas of the world is difficult to ascertain.

Competencias médicas y su evaluación al egreso de la carrera de medicina en la Universidad Nacional de Cuyo (Argentina) / Medical competences and their assessment at the end of the undergraduate medical program at the National University of Cuyo (Argentina)

Los alumnos de la Carrera de Medicina, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, deben aprobar para su egreso, una Prueba Global de Ciclo Clínico. Con el objeto de analizar qué evaluar y qué instrumentos utilizar, se diseñó este trabajo tomando como marco teórico la Educación Basada en Competencias, en la que el curriculum debe ajustar el proceso de aprendizaje a los resultados esperados. Se entrevistó a médicos, pacientes, enfermeros, empleadores, docentes y alumnos (N=147). Se definieron seis competencias médicas y 51 componentes en total. Con esta información se realizó una encuesta a docentes (N=50) y se evaluó la significatividad de las diferencias de las respuestas obtenidas. Esto permitió reestructurar y reducir a 27 los componentes de las competencias. Se realizó una última consulta con la técnica Delphi (N=40), con el objeto de elegir el instrumento para evaluar cada componente y el momento de la carrera para hacerlo. De los veintisiete, veinticuatro deberían evaluarse durante el ciclo clínico, dieciséis al finalizar la carrera y tres en primer año. Los instrumentos más elegidos fueron: observación del desempeño con pacientes, evaluación continua con retroalimentación y exámenes orales y escritos. A partir de estos resultados, se dispone de una definición de las competencias y sus componentes para el ejercicio profesional, una selección de los instrumentos y el momento de la carrera en que deben evaluarse, el aval de la comunidad educativa para ambos productos y una base para establecer un sistema de evaluación para todo el curriculum (AU)

In order to graduate, medical students at the National University of Cuyo have to pass a mandatory global clinical exam. This research project was designed to analyze what that exam should assess as well as the instruments to be used. The project employed the paradigm of Outcome-Based Education, which establishes that the curriculum must adjust the learning process and the assessment tools to the expected outcomes. An interview, conducted with physicians, patients, nurses, employers, faculty members and students (n=147) defined six competences with a total of fifty-one components. The six competences were: Clinical skills; Medical knowledge; Communication skills; Personal and professional update and development; Ethical and legal aspects of the profession; and Social context and health system. A survey was drafted to select the essential components of the six competences. This survey was applied to fifty faculty members. The significance of the differences was studied. As a result the competence components were reordered and reduced to twenty-seven. A second survey, based on the Delphi technique, was submitted to another group of faculty members (n=40), in order to select the most appropriate assessment instrument for each component and to determine the most adequate timetable for such assessments during the course of the medical program. Twenty-four of the twenty-seven components were to be evaluated during the clinical years (sixteen of them to be assessed after the internship, at the end of the medical program) and three were to be appraised during the first year. Observation of the students' performance with patients, continuous evaluation with feedback, and oral and written exams were the instruments deemed most appropriate by the faculty. In conclusion, this project served to define the most appropriate competences and their components for a professional medical practice, as well as determining the assessment instruments and the timetable for their application. It also obtained faculty support and established the framework of a global system for student assessment across the curriculum (AU)

Análisis epidemiológico de 970 pacientes con fisura labio-alvéolo-palatina con tratamiento prequirúrgico: Argentina 2009 / Epidemiological analysis of 970 patients with cleft lip, alveolus palate with presurgical treatment

Las fisuras labio-alvéolo-palatinas (FLAP) son anomalías congénitas que tienen una frecuencia estimada, mundial, de 1/500 a 1/2500 nacidos vivos y una etiología que involucra factores genéticos, ambientales. Objetivo General: Estudiar la complejidad de la rehabilitación del paciente FLAP que concurre a servicios adheridos a la Red. Metodología: la Red de Servicios de Rehabilitación de pacientes FLAP, diseñada y organizada en la primera etapa del proyecto ha proporcionado por medio de su registro epidemiológico la información básica de 970 pacientes. Resultados: La fisura de paladar con labio fisurado (Q.37) es el diagnóstico más frecuente con el 70 por ciento, la fisura de paladar (Q.35) el 17,8 por ciento y labio fisurado (Q36) 11,3 por ciento. En el 20,3 por ciento de los casos hubo malformaciones asociadas. La colocación de "placa ortopédica" y "placa con tutor nasal" fueron aplicados en el 83 por ciento de los casos. La cirugía de labio en el 60 por ciento de los casos fue realizada en tiempo y oportunidad, antes de los 6 meses de vida. En "labio unilateral" el tipo de cirugía más empleado fue de "rotación y avance" en el 40 por ciento. El 70 por ciento (32) de los casos de niños de 1 a 8 años de edad recibió "Cirugía Secundaria".

Oral clefts, in particular clefts lip and palate, are mayor birth defects with a variable prevalence ranging from 1 in 500 to 1 in 2500 newborns. Oral clefts include syndromic or isolated forms; both genes and environmental exposures are involved in their complex etiology. Objective: The objective of the present study is to organize a network of rehabilitation services of patients with FLAP. Methodology: The Network of Rehabilitation Services, designed and organized in the first phase of the project, has provided basic information of 970 patients by means of one epidemiologic register. Results: Palatal fissure with fissured lip (Q.37) is the most frequent diagnostic with 70 per cent of the cases; palatal fissure (Q35) with 17.8 per cent, and fissured lip (Q36) with 11.3 per cent. In 20.3 per cent of cases there were associated malformations. Placing of "orthopaedic plate" and "plate with nasal tutor" was applied to 83 per cent of the cases. The 60 per cent of surgery of lip was made in time and opportunity, before the 6 months of life. The most utilized method of surgery in "unilateral lip" was "rotation and advance" in 40 per cent of the cases. The 70 per cent (32) of the cases of children from 1 to 8 years old have received “Secondary Surgery”.