Análisis del proceso técnico político de la ordenanza municipal para promoción de salud de Quillota

RESUMEN Para contribuir a la vida sana de la comunidad y en atención a las recomendaciones nacionales e internacionales para combatir la obesidad y sus consecuencias, en 2017 la Municipalidad de Quillota promulgó una Ordenanza de Promoción de Salud para favorecer entornos alimentarios saludables y para la práctica de actividad física. No está descrito en qué consiste y cuáles son las dificultades para establecer este tipo de normativas locales. El objetivo de este estudio fue analizar el proceso técnico y político que culminó en la generación de esta Ordenanza como ejemplo para el resto de los municipios del país. Con un diseño cualitativo, exploratorio y retrospectivo se recolectó información a través de entrevistas, grupos focales y diálogos participativos. Se realizó un mapeo de actores y el análisis de las lecciones aprendidas, considerando barreras y facilitadores. Los resultados muestran que la Ordenanza representó un desafío para la toma de decisiones que habilitaron su consolidación tanto en términos de gestión técnica como en los niveles de poder. Entre las lecciones aprendidas destaca la relevancia de un escenario político favorable, un equipo técnico competente y con liderazgo, y la fuerte articulación intersectorial; siendo clave la voluntad de las autoridades municipales y la negociación con sectores de oposición. La participación comunitaria activa fue un punto de compleja implementación.

ABSTRACT With the aim of improving the health of the community and given national and international recommendations to combat obesity and its consequences, in 2017, the Municipality of Quillota enacted a Health Promotion Ordinance to promote healthy food environments and physical activity practices. The ordinance is not specifically detailed, nor are the difficulties in establishing such local regulations described. Thus, this study intended to analyze the technical and political processes that generated this ordinance, which may serve as an example for other municipalities. The information collection was made through interviews, focus groups, and participatory dialogues, using a qualitative, exploratory, and retrospective design. Actors mapping and lessons learned analysis, considering barriers and facilitators found, was conducted. The results show that the ordinance consolidation presented a challenge to the decision-making management at the technical and empowerment levels. Lessons learned include favorable political scenarios, a competent technical team, and strong cross-sectoral articulation. Two key factors were the municipal authorities' resolution and negotiation with opposition sectors. Active community participation was a point of complex implementation.

Prognostic value of mutations in isocitrate dehydrogenase 1 (IDH1) and reverse telomerase transcriptase (TERT ) in Argentine patients` gliomas / Valor pronóstico de mutaciones en Isocitrato dehidrogenasa1 (IDH1) y Telomerasa transcriptasa reversa (TERT ) en gliomas de pacientes argentinos

Background and aim: Gliomas are the most common primary brain tumors, classified according to their histopathological and genetic features. Tumorigenesis depends on alterations in different genes. The aim of this study was the identification of mutations in IDH1 and TERT genes in gliomas of Argentine patients and to correlate them with clinical features and prognosis. Methods: DNA was isolated from 19 biopsies with different glioma grades matched with blood samples. IDH1 and TERT mutations were studied by PCR amplifica-tion and sequencing. Results: Six out of seven patients with low-grade glioma (grade II) harbor IDH1 mutations, mainly without tumor growth and overall survival of more than 12 months. Eleven out of twelve patients with high-grade gliomas (grade III/IV) showed wild type IDH1, mainly with tumor growth and shorter survival than low-grade gliomas. Mutated TERT promoter was present in 5 out of 11 high-grade gliomas, showing the prevalence of polymorphic C allele. In 1 out of 5 low-grade gliomas with a predominance of T allele. TERT and IDH1 mutations were mutually exclusive in most gliomas. Conclusions: Our results show that genetic tests provided a more accurate prognosis than histopathological analysis. The evolution of gliomas can be predicted primarily by the mutational status of IDH1 and secondarily by other markers, such as TERT mutational status

Antecedentes y objetivo: los gliomas son los tumores cerebrales primarios más comunes y se clasifican según sus características histopatológicas y genéticas. La tumorigénesis depende de alteraciones en diferentes genes. El objetivo de este estudio fue identificar mutaciones en los genes IDH1 y TERT en gliomas de pacientes argentinos y correlacionarlos con la evolución clínica. Métodos: se obtu-vieron 19 muestras pareadas de ADN de gliomas y de la sangre. Las mutaciones en IDH1 y TERT se analizaron por PCR y secuenciación. Resultados: la IDH1 mutada se encontró en 6 de los 7 gliomas de bajo grado (grado II), mayormente sin crecimiento tumoral y una sobrevida mayor de 12 meses. La IDH1 salvaje estaba presente en 11 de los 12 gliomas de alto grado (grado III y IV) mayormente con crecimiento tumoral y menor sobrevida que los tumores de bajo grado. Las mutaciones en el promotor del gen TERT se observaron en 5 de los 11 gliomas de alto grado, con la prevalencia de alelo polimórfico C, en cambio, en gliomas de bajo grado TERT mutado estaba presente en 1 de los 5 gliomas con predominio del alelo T. Las mutaciones en IDH1 y TERT fueron mutuamente excluyentes en la mayoría de los gliomas. Conclusiones: el análisis genético provee un pronóstico más certero que el análisis histopatológico. Nuestros resulta-dos muestran que la evolución de gliomas puede predecirse primariamente por el estado mutacional de IDH1 y secundariamente por mutaciones en otros marcadores tales como el TERT

Small mutation screening in the DMD gene by whole exome sequencing of an argentine Duchenne/Becker muscular dystrophies cohort.

Dystrophinopathies are neuromuscular X-linked recessive diseases caused by mutations in the DMD gene. This study aimed to identify DMD gene small mutations by Whole Exome Sequencing (WES), in order to confirm clinical diagnosis, identify candidates for Ataluren treatment and perform carrier status testing. Furthermore, was our goal to characterize the DMD sequence variants and identify ancestral haplotypes. We analyzed 40 non-related individuals (38 affected boys with dystrophinopathy presumptive clinical diagnosis and 2 at-risk women) with negative MLPA results. Pathogenic DMD variants were found in 32 boys. Surprisingly, in another 4 patients with absence/deficiency of dystrophin in muscle biopsy, pathogenic variants were found in Limb-girdle muscular dystrophy genes. Therefore, the WES detection rate resulted ∼94% (36/38). We could identify 15 Ataluren candidates and exclude 2 at-risk women. The characterization of the occurrence and diversity of DMD sequence variants from our cohort and from LOVD database, revealed no hotspots but showed exons/introns unlikely to carry small molecular alterations and exons presenting a greater mutagenic abundance than others. Also, we have detected the existence of 2 co-segregating haplotypes blocks. Finally, this work represents the first DMD gene small mutations screening applying WES in an argentine cohort, contributes with the characterization of our population and collaborates with the DMD small mutation's knowledge.

RB1 gene mutations in Argentine retinoblastoma patients. Implications for genetic counseling.

Retinoblastoma (RB) is an inherited childhood ocular cancer caused by mutations in the tumor suppressor RB1 gene. Identification of RB1 mutations is essential to assess the risk of developing retinoblastoma in the patients´ relatives. Retinoblastoma is a potentially curable cancer and an early diagnosis is critical for survival and eye preservation. Unilateral retinoblastoma is mostly non-heritable and results from two somatic mutations whereas bilateral retinoblastoma is heritable and results from one germline and one somatic mutation, both have high penetrance, 90%. The purpose of this study was to identify causative RB1 mutations in RB patients with different clinical presentations. A comprehensive approach was used to study a cohort of 34 patients with unilateral, bilateral and trilateral retinoblastoma. Blood and tumor DNA was analyzed by sequencing and multiplex ligation-dependent probe amplification (MLPA) assay. Validation of an insertion mutation was performed by cloning the PCR product. Most of the patients in our cohort had unilateral RB, eight patients had bilateral RB and one patient had a trilateral tumor with ocular and suprasellar/sellar locations. Other tumors in addition to retinoblastoma were also found in the affected families. One patient had two syndromes, retinoblastoma and schwannomatosis, and another RB patient had a father with a retinoma. Five out of the 25 unilateral RB patients carried germinal mutations (20%), which were mostly missense mutations. The bilateral and trilateral patients carried splice-site, nonsense and frameshift mutations as well as a whole RB1 gene deletion. Missense mutations were associated with mild phenotype: unilateral retinoblastoma, retinoma or no tumor. In this study we identified causative RB1 mutations in most bilateral RB patients and in some unilateral RB patients, including five novel mutations. These data are crucial for genetic counseling and confirm the need to perform complete genetic screening for RB1 mutations in both constitutional and tumor tissues.

MLPA analysis of an Argentine cohort of patients with dystrophinopathy: Association of intron breakpoints hot spots with STR abundance in DMD gene.

Dystrophinopathies are X-linked recessive diseases caused by mutations in the DMD gene. Our objective was to identify mutations in this gene by Multiplex Ligation Probe Amplification (MLPA), to confirm the clinical diagnosis and determine the carrier status of at-risk relatives. Also, we aimed to characterize the Dystrophinopathies argentine population and the DMD gene. We analyzed a cohort of 121 individuals (70 affected boys, 11 symptomatic women, 37 at-risk women and 3 male villus samples). The MLPA technique identified 56 mutations (45 deletions, 9 duplications and 2 point mutations). These results allowed confirming the clinical diagnosis in 63% (51/81) of patients and symptomatic females. We established the carrier status of 54% (20/37) of females at-risk and 3 male villus samples. We could establish an association between the most frequent deletion intron breakpoints and the abundance of dinucleotide microsatellites loci, despite the underlying mutational molecular mechanism remains to be elucidated. The MLPA demonstrate, again, to be the appropriate first mutation screening methodology for molecular diagnosis of Dystrophinopathies. The reported results permitted to characterize the Dystrophinopathies argentine population and lead to better understanding of the genetic and molecular basis of rearrangements in the DMD gene, useful information for the gene therapies being developed.

Molecular diagnosis of dystrophinopathies using a multi-technique analysis algorithm.

INTRODUCTION: Dystrophinopathies are X-linked recessive neuromuscular diseases caused by mutations in the dystrophin gene. In this study we aimed to detect mutations within the dystrophin gene in DMD patients, to determine the carrier status of women, and to perform a prenatal diagnosis. METHODS: We analyzed 17 individuals from 2 unrelated families with a history of DMD. We used multiplex PCR, multiplex ligation-dependent probe amplification (MLPA), and short tandem-repeat (STR) segregation analysis to accurately detect and characterize the mutations and to identify the at-risk haplotype. RESULTS: The selected methodology allowed for characterization of 2 single-exon out-of-frame deletions in affected patients. Nine of 13 women and a fetus were excluded from being carriers. Three recombination events were found and suggested that germline mosaicism had occurred in both families. CONCLUSIONS: This methodology proved to be efficient for characterizing the disease-causing mutation in affected individuals and for assessing the carrier status in healthy relatives. These findings helped inform precise genetic counseling and contributed to characterization of the disease in the Argentine population.

Spectrum of RB1 mutations in argentine patients: 20-years experience in the molecular diagnosis of retinoblastoma.

BACKGROUND: Retinoblastoma is a hereditary cancer of childhood caused by mutations in the RB1 tumor suppressor gene. An early diagnosis is critical for survival and eye preservation, thus identification of RB1 mutations is important for unequivocal diagnosis of hereditary retinoblastoma and risk assessment in relatives. METHODS: We studied 144 families for 20 years, performing methodological changes to improve detection of mutation. Segregation analysis of polymorphisms, MLPA, FISH and cytogenetic assays were used for detection of "at risk haplotypes" and large deletions. Small mutations were identified by heteroduplex/DNA sequencing. RESULTS: At risk haplotypes were identified in 11 familial and 26 sporadic cases, being useful for detection of asymptomatic carriers, risk exclusion from relatives and uncovering RB1 recombinations. Ten large deletions (eight whole gene deletions) were identified in six bilateral/familial and four unilateral retinoblastoma cases. Small mutations were identified in 29 cases (four unilateral retinoblastoma patients), being the majority nonsense/frameshift mutations. Genotype-phenotype correlations confirm that the retinoblastoma presentation is related to the type of mutation, but some exceptions may occur and it is crucial to be considered for genetic counseling. Three families included second cousins with retinoblastoma carrying different haplotypes, which suggest independent mutation events. CONCLUSION: This study enabled us to obtain information about molecular and genetic features of patients with retinoblastoma in Argentina and correlate them to their phenotype.

Prenatal diagnosis of Duchenne/Becker muscular dystrophy by short tandem repeat segregation analysis in Argentine families.

INTRODUCTION: Duchenne/Becker muscular dystrophies (DMD/BMD) are X-linked recessive diseases caused by mutations in the dystrophin gene. METHODS: We used multiplex polymerase chain reaction (PCR) and short tandem repeat (STR) segregation analysis for DMD/BMD-carrier detection and prenatal diagnosis. RESULTS: Twenty-four at-risk pregnancies were evaluated: 17 were excluded from carrying dystrophin gene mutations with 95-100% certainty. Of the remaining cases, 2 were determined to carry a dystrophin gene mutation with 95-100% certainty. Three cases had a 67% probability of carrying the mutation, and 2 others were not informative. The certainty of the test increased to ~100% in some cases due to the identification of several genetic events: 4 recombinations; 4 de novo mutations; and 8 deletions encompassing some of the STRs evaluated. DISCUSSION: Overall, 19 of 24 (79%) molecular prenatal diagnoses were informative, indicating that multiplex PCR/STR segregation analysis is a reliable method for carrier detection and prenatal diagnosis when other more sophisticated techniques are unavailable.

Neurofibromatosis type 2: molecular and clinical analyses in Argentine sporadic and familial cases.

Neurofibromatosis 2 is a familial syndrome characterized by the development of schwannomas, meningiomas and ependymomas. Most of them are benign however, their location in the nervous system has harmful effects on important cranial and spinal structures. These tumors are developed as the outcome of NF2 gene (22q12) inactivation. The NF2 protein, merlin or schwannomin belongs to the Ezrin, Radixin, Moesin (ERM) family involved in the cytoskeletal network and has a tumor suppressor function. Inactivating mutations occur as "de novo" (more frequently) or as inherited, and most of them are frameshift or nonsense. Our aim is to study NF2 gene alterations in Argentine patients and relate them to clinical features. 10 families and 29 single patients were analyzed for: 1) at-risk haplotype by STR-segregation analysis and 2) NF2 gene mutations by SSCP/heteroduplex/sequencing. The at-risk haplotype was uncovered in 8 families and mutations were identified in 5 patients. The molecular data are in full agreement with the clinical features supporting previous reports. The obtained results were important for the detection of mutation-carrying relatives and exclusion of other individuals from risk.

Combined cytogenetic and molecular analyses for the diagnosis of Prader-Willi/Angelman syndromes.

Prader-Willi (PWS) and Angelman (AS) are syndromes of developmental impairment that result from the loss of expression of imprinted genes in the paternal (PWS) or maternal (AS) 15q11-q13 chromosome. Diagnosis on a clinical basis is difficult in newborns and young infants; thus, a suitable molecular test capable of revealing chromosomal abnormalities is required. We used a variety of cytogenetic and molecular approaches, such as, chromosome G banding, fluorescent in situ hybridization, a DNA methylation test, and a set of chromosome 15 DNA polymorphisms to characterize a cohort of 27 PWS patients and 24 suspected AS patients. Molecular analysis enabled the reliable diagnosis of 14 PWS and 7 AS patients, and their classification into four groups: (A) 6 of these 14 PWS subjects (44 %) had deletions of paternal 15q11-q13; (B) 4 of the 7 AS patients had deletions of maternal 15q11-q13; (C) one PWS patient (8 %) had a maternal uniparental disomy (UPD) of chromosome 15; (D) the remaining reliably diagnoses of 7 PWS and 3 AS cases showed abnormal methylation patterns of 15q11-q13 chromosome, but none of the alterations shown by the above groups, although they may have harbored deletions undetected by the markers used. This study highlights the importance of using a combination of cytogenetic and molecular tests for a reliable diagnosis of PWS or AS, and for the identification of genetic alterations.

Inequalities in health in Latin America and the Caribbean: descriptive and exploratory results for self-reported health problems and health care in twelve countries

Objective: To explore and describe inequalities in health and use of health care as revealed by self-report in 12 countries of Latin America and the Caribbean. Methods: A descriptive and exploratory study was performed based on the responses to questions on health and health care utilization that were included in general purpose household surveys. Inequalities are described by quintile of household expenditures (or income) per capita, sex, age group (children, adults, and older adults), and place of residence (urban vs. rural area). For those who sought health care, median polishing was performed by economic status and sex, for the three age groups. Results: Although the study is exploratory and descriptive, its findings show large economic gradients in health care utilization in these countries, with generally small difference between males and females and higher percentages of women seeking health care than men, although there were some exceptions among the lower economic strata in urban areas. Conclusions: Inequalities in self-reported health problems among the different economic strata were small, and such problems were usually more common among women than men. The presence of small inequalities may be due to cultural and social differences in the perception of health. However, in most countries included in the study, large inequalities were found in the use of health care for the self-reported health problems. It is important to develop regional projects aimed at improving the questions on self-reported health in household interview surveys so that the determinants of the inequalities in health can be studied in depth. The authors conclude that due to the different patterns of economic gradients among different age groups, and among males and females, the practice of standardization used in constructing concentration curves and in computing concentration indices should be avoided. At the end is a set of recommendations on how to improve these sources of data. Despite their shortcomings, household interview surveys are very useful in understanding the dimensions of health inequalities in these countries (AU)

Inequalities in health in Latin America and the Caribbean: descriptive and exploratory results for self-reported health problems and health care in twelve countries / Desigualdades de salud en América Latina y el Caribe: resultados descriptivos y exploratorios basados en la autonotificación de problemas de salud y atención de salud en doce países

Objective. To explore and describe inequalities in health and use of health care as revealed by self-report in 12 countries of Latin America and the Caribbean. Methods. A descriptive and exploratory study was performed based on the responses to questions on health and health care utilization that were included in general purpose household surveys. Inequalities are described by quintile of household expenditures (or income) per capita, sex, age group (children, adults, and older adults), and place of residence (urban vs. rural area). For those who sought health care, median polishing was performed by economic status and sex, for the three age groups. Results. Although the study is exploratory and descriptive, its findings show large economic gradients in health care utilization in these countries, with generally small differences between males and females and higher percentages of women seeking health care than men, although there were some exceptions among the lower economic strata in urban areas. Conclusions. Inequalities in self-reported health problems among the different economic strata were small, and such problems were usually more common among women than men. The presence of small inequalities may be due to cultural and social differences in the perception of health. However, in most countries included in the study, large inequalities were found in the use of health care for the self-reported health problems. It is important to develop regional projects aimed at improving the questions on selfreported health in household interview surveys so that the determinants of the inequalities in health can be studied in depth. The authors conclude that due to the different patterns of economic gradients among different age groups and among males and females, the practice of standardization used in constructing concentration curves and in computing concentration indices should be avoided. At the end is a set of recommendations on how to improve these sources of data. Despite their shortcomings, household interview surveys are very useful in understanding the dimensions of health inequalities in these countries

Objetivo. Explorar y describir las desigualdades detectadas a partir de la autonotificación de problemas de salud y de la búsqueda de atención sanitaria en 12 países de América Latina y el Caribe. Métodos. Se analizan las preguntas sobre los problemas de salud y la búsqueda de atención en encuestas de hogares de tipo general y se describen las desigualdades correspondientes de acuerdo con quintiles de gasto (o ingreso) doméstico per cápita, sexo, grupo de edad (niños, adultos y adultos mayores) y área urbana o rural. En el caso de las personas que buscaron atención de salud, se aplica la técnica de pulimiento de medianas por nivel económico y sexo para los tres grupos de edad. Resultados. Aun cuando el trabajo es exploratorio y descriptivo, los resultados muestran en los países estudiados la existencia de importantes gradientes en la utilización de servicios de salud según nivel económico, y la presencia de diferencias generalmente pequeñas entre hombres y mujeres, con algunas excepciones en los estratos económicos más bajos en áreas urbanas. Conclusiones. Las desigualdades detectadas a partir de la autonotificación de problemas de salud son muy pequeñas entre personas de diferente nivel económico y los problemas suelen ser más frecuentes entre las mujeres que entre los hombres. Esto se debe posiblemente a diferencias culturales y sociales en la percepción de la salud. Las desigualdades en la búsqueda de atención son grandes en la mayoría de los países estudiados. Es muy importante que se desarrollen proyectos regionales encaminados a mejorar las preguntas para la autonotificación de problemas de salud con el fin de poder estudiar a fondo los factores que determinan las desigualdades en el ámbito sanitario. Los autores concluyen que debido a que los gradientes económicos muestran patrones diferentes en los distintos grupos de edad y en hombres y mujeres, los datos no deben estandarizarse a la hora de derivar curvas de concentración y calcular los índices de concentración. Al final hay una lista de recomendaciones sobre cómo mejorar estas fuentes de datos. Pese a sus deficiencias, las encuestas de hogares nos ayudan a entender las complejidades de las desigualdades de salud en estos países.