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Introducción: El cáncer de pulmón (CP) es una enfermedad con gran impacto a nivel mundial en el número de muertes y en costos en salud. La alta incidencia y mortalidad de esta enfermedad asociada al diagnóstico tardío, y la mejoría del pronóstico ante una detección temprana, determinan que sea una patología pasible de beneficiarse mediante detección temprana. La tomografía de baja dosis de radiación (TCBD) demostró ser un método que se pue- de realizar periódicamente a un grupo de personas con alto riesgo de desarrollar CP y así reducir la mortalidad por esta enfermedad. Sin embargo, este beneficio es tal cuan- do se encuentra desarrollado bajo un programa organizado y con participación multi- disciplinaria especializada en cáncer de pulmón. Métodos: Se plantea determinar lineamientos básicos para el desarrollo de la detección temprana de cáncer de pulmón en América Latina para que pueda ser realizada en forma uniforme, con el menor riesgo y el máximo beneficio esperado. Se analizaron las principales publicaciones referidas a este tema, contemplando la diversidad de atención y acceso de América Latina. Resultado: Se desarrollan requerimientos mínimos para la implementación de un pro- grama. Discusión: El número de programas en la región es escaso y depende más de esfuerzos individuales que de políticas generales de salud. Consideramos que estos lineamien- tos pueden servir de apoyo para el desarrollo de más programas en la región y de for- ma más homogénea.

Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early de- tection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more ho- mogeneous way.

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BACKGROUND: Lung cancer (LC) screening improves LC survival; the best screening method in terms of improving survival is low-dose CT (LDCT), outpacing chest X-ray and sputum cytology. METHODS: A consensus of experts in Argentina was carried out to review the literature and generate recommendations for LC screening programmes. A mixed-method study was used with three phases: (1) review of the literature; (2) modified Delphi consensus panel; and (3) development of the recommendations. The Evidence to Decision (EtD) framework was used to generate 13 evaluation criteria. Nineteen experts participated in four voting rounds. Consensus among participants was defined using the RAND/UCLA method. RESULTS: A total of 16 recommendations scored ≥7 points with no disagreement on any criteria. Screening for LC should be performed with LDCT annually in the population at high-risk, aged between 55 and 74 years, regardless of sex, without comorbidities with a risk of death higher than the risk of death from LC, smoking ≥30 pack-years or former smokers who quit smoking within 15 years. Screening will be considered positive when finding a solid nodule ≥6 mm in diameter (or ≥113 mm3) on baseline LDCT and 4 mm in diameter if a new nodule is identified on annual screening. A smoking cessation programme should be offered, and cardiovascular risk assessment should be performed. Institutions should have a multidisciplinary committee, have protocols for the management of symptomatic patients not included in the programme and distribute educational material. CONCLUSION: The recommendations provide a basis for minimum requirements from which local institutions can develop their own protocols adapted to their needs and resources.

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Objective: Evaluate the prevalence of asthma risk in subject of 13-14 years old that were exposed to volcanic ash. One year after the eruption of the Calbuco Volcano and in 2 cities with different degrees of exposure. Methods: Cross-sectional study was developed in subjects of 13-14 years old of two Patagonian cities: San Carlos de Bariloche and Cipolletti. The ISAAC questionnaire and video questionnaire was applied to determine asthma risk. Demographic and perception of exposure variables were assessed. Results: 511 subjects were surveyed in both cities. The prevalence of asthma at risk symptoms was higher in Bariloche 14% compared to Cipolletti 10%, but this difference was not statistically significant (p=0.32). A significant increase in the perception of volcanic ash exposure was reported 14% in Bariloche city vs. 6% in Cipolletti city, p<0.05. Conclusions: After 18 months of volcanic eruption with respiratory ash exposure and the lack of respiratory symptoms difference between two cities with different degree of exposure, this factor may not contribute to have a clinical impact in respiratory health.

Objetivo: Evaluar la prevalencia de riesgo de asma en adolescentes expuestos a ceniza volcánica a un año de la erupción del Volcán Calbuco, en 2 ciudades con diferentes grado de afectación. Métodologia: Estudio de Corte Transversal, en adolescentes de 13-14 años en dos ciudades con diferente grado de exposición a ceniza volcánica: San Carlos de Bariloche y Cipolletti. Se aplicó cuestionario y video-cuestionario ISAAC para determinar riesgo de asma. Las variables demográficas y percepción de exposición, se obtuvieron por cuestionario previo a la aplicación de metodología ISAAC. Resultados: Se encuestaron 511 sujetos en total. Se reportó prevalencia de síntomas de riesgo de asma en Bariloche resultó de 14% comparado con Cipolletti que reportó 10% (p=0.32). Se informó mayor exposición a ceniza volcánica en la ciudad de Bariloche vs. Cipolletti; 14% y 6% respectivamente con p<0.05. Conclusiones: La falta diferencia estadisticamente significativa respecto a la prevalencia de sintomas de riesgo de asma entre ambas poblaciones con diferente nivel de exposición y tras 18 meses de la erupción volcánica mas exposición respiratoria a ceniza volcánica, pareciera no presentar impacto clínico en la salud respiratoria.

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Neuropathic and inflammatory pain results from cellular and molecular changes in dorsal root ganglion (DRG) neurons. The type-2 receptor for Angiotensin-II (AT2R) has been involved in this type of pain. However, the underlying mechanisms are poorly understood, including the role of the type-1 receptor for Angiotensin-II (AT1R). Here, we used a combination of immunohistochemistry and immunocytochemistry, RT-PCR and in vitro and in vivo pharmacological manipulation to examine how cutaneous inflammation affected the expression of AT1R and AT2R in subpopulations of rat DRG neurons and studied their impact on inflammation-induced neuritogenesis. We demonstrated that AT2R-neurons express C- or A-neuron markers, primarily IB4, trkA, and substance-P. AT1R expression was highest in small neurons and co-localized significantly with AT2R. In vitro, an inflammatory soup caused significant elevation of AT2R mRNA, whereas AT1R mRNA levels remained unchanged. In vivo, we found a unique pattern of change in the expression of AT1R and AT2R after cutaneous inflammation. AT2R increased in small neurons at 1 day and in medium size neurons at 4 days. Interestingly, cutaneous inflammation increased AT1R levels only in large neurons at 4 days. We found that in vitro and in vivo AT1R and AT2R acted co-operatively to regulate DRG neurite outgrowth. In vivo, AT2R inhibition impacted more on non-peptidergic C-neurons neuritogenesis, whereas AT1R blockade affected primarily peptidergic nerve terminals. Thus, cutaneous-induced inflammation regulated AT1R and AT2R expression and function in different DRG neuronal subpopulations at different times. These findings must be considered when targeting AT1R and AT2R to treat chronic inflammatory pain. Cover Image for this issue: doi: 10.1111/jnc.14737.

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Antecedentes: Las personas expuestas a cenizas volcánicas presentan incremento de los síntomas respiratorios. La duración de la exposición, las características y concentración de la ceniza son determinantes en el impacto sobre la salud respiratoria. Objetivos: Describir la prevalencia de sibilancias en el último año en la población adulta expuesta a la caída de ceniza volcánica en dos ciudades con diferente nivel de exposición. Secundariamente describir la prevalencia de síntomas oculares y respiratorios en esas poblaciones. Materiales y métodos: Se realizó estudio de corte transversal cinco días después de la erupción del volcán Calbuco, en dos ciudades patagónicas con diferente nivel de exposición (alta y baja exposición). La prevalencia de sibilancias, síntomas respiratorios y oculares, se evaluaron mediante la encuesta telefónica por sistema interactivo de voz. Resultados: La prevalencia de sibilancias fue similar en las ciudades de baja y alta exposición (30.2% vs. 31.0%; p: 0.82). Los síntomas respiratorios y los síntomas oculares fueron 32% y 57% respectivamente (p: NS). Conclusión: Luego de la erupción del volcán Calbuco, una alta proporción de la población expuesta reportó sibilancias, síntomas respiratorios y oculares. No se demostraron diferencias entre las ciudades analizadas. La prevalencia de sibilancias fue mayor en estas ciudades que la reportada a nivel nacional. Síntomas respiratorios, prevalencia de sibilancias en adultos mayor a lo reportado por a nivel nacional.

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History: People exposed to volcanic ash show increased respiratory symptoms. The duration of exposure, the characteristics and ash concentration are determinants of the impact on respiratory health. Objectives: To describe the prevalence of wheezing over the past year within the adult population exposed to volcanic ash spilling in two cities with different levels of exposure. Secondarily, to describe the prevalence of ocular and respiratory symptoms in those populations. Materials and methods: A cross-sectional study was conducted five days after the eruption of the Calbuco volcano in two Patagonian cities with different levels of exposure (high and low levels of exposure). The prevalence of wheezing and respiratory and ocular symptoms was evaluated by means of telephone surveys conducted through an interactive voice response system. Results: The prevalence of wheezing was similar both in cities with low and with high levels of exposure (30.2% vs. 31.0%; p: 0.82). The respiratory and ocular symptoms were 32% and 57%, respectively (p: NS). Conclusion: After the eruption of the Calbuco volcano, a high proportion of the exposed population showed wheezing and respiratory and ocular symptoms. No differences were shown between the analyzed cities. The prevalence of wheezing in these cities was higher than that reported on the national level. The respiratory symptoms and the prevalence of wheezing in adults were higher than those reported on the national level.

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AT2 receptor (AT2R) plays a functional role in foetal development. Its expression declines in most tissues soon after birth but stays high in sensory areas of the adult nervous system. In the dorsal root ganglia (DRG) the expression pattern of AT2R during development and the identity of the subpopulation expressing it remain unknown. Using a combination of semi-quantitative PCR, western blotting and immunohistochemistry we examined the expression of AT2R at mRNA and protein levels in rat DRGs from embryonic day 15 (E15) until postnatal day 30 (PN30). We found that both AT2R mRNA and protein levels exhibited only minor (statistically non-significant) fluctuations from E15 to PN30. Detailed quantitative analysis of ABC/DAB AT2R staining showed a) that the receptor was present in most neurons at E15 and E18 and b) that postnatally it was predominantly expressed by small DRG neurons. Given that small neurons are putative C-nociceptors and the proposed role of AT2R in neuropathic pain, we next examined whether these AT2R-positive neurons co-localized with Ret and trkA embryonically and with IB4-binding postnatally. Most AT2R-positive neurons expressed trkA embryonically and bound IB4 postnatally. We found strong positive statistically highly significant correlations between AT2R cytoplasmic%intensities and trkA at E15/E18 and with Ret only at E18. Cytoplasmic AT2R also strongly and positively correlated with IB4-binding at PN3, 15 and 30. Our demonstration that a subpopulation of C-nociceptor-like neurons expresses AT2R during development supports a role for this receptor in neuropathic pain.

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Introducción: Las erupciones volcánicas tienen diversos impactos sobre la salud de la población expuesta y el sistema respiratorio es uno de los más afectados debido a la inhalación de los productos volatilizados. Estudios experimentales en ratones demostraron que la exposición crónica a ceniza volcánica de la erupción del complejo Puyehue-Caulle se asoció con respuesta inflamatoria de la vía aérea. A la fecha, no se ha reportado el impacto sobre la salud respiratoria de los niños expuestos a este evento. Objetivo: Determinar la prevalencia de síntomas de asma en niños 2 años después de la erupción del complejo Puyehue-Caulle. Materiales y Métodos: Se realizó un estudio de corte transversal en niños de 13 y 14 años asistentes a 11 colegios secundarios de la Ciudad de San Carlos de Bariloche, Rio Negro. Se encuestaron usando los cuestionarios ISAAC, y se realizaron mediciones de espirometría y monóxido de carbono en aire espirado a cada uno de los sujetos. Resultados: Se encuestaron 303 sujetos, 56% fueron varones y 47% asistían a escuelas del sector público. El 12,8 % reportaron ser fumadores activos. El cuestionario ISAAC más video-cuestionario reportó 27% de sibilancias alguna vez en la vida y 14% de sibilancias en el último año. El análisis de las espirometrías mostró 1% de la muestra con patrón obstructivo. Conclusiones: En una muestra de niños residentes de una ciudad con alto nivel de exposición a ceniza volcánica se observó una alta prevalencia de síntomas de asma, los mismos fueron significativamente más prevalentes que en estudio previo realizado en esa ciudad.

Background: Volcanic eruptions have different health impacts on exposed population and the respiratory system is one of the most affected due to the inhalation of volatilized products. Experimental studies in guinea pigs showed that chronic exposure to volcanic ash from the eruption of the Puyehue-Caulle complex is associated with inflammatory airway response. To date, it has not been reported respiratory health impact of children exposed to this. Objective: To determine children´s asthma symptoms prevalence 2 years after Puyehue-Caulle complex´s eruption. Methods: Cross-sectional study was conducted among 13 and 14 years old children attending 11 secondary schools in San Carlos de Bariloche City, Rio Negro. They were surveyed with ISAAC´s questionnaires and spirometry and carbon monoxide in exhaled air measurements were performed to each subject. Results: 303 subjects were surveyed, 56% were male and 47% belonged to public schools. 12,8% were active tobacco smokers, 27% had wheezing sometime in the life and 14% had wheezes in the last year (based on ISAAC questionnaire). Only 1% of the spirometry had airway obstruction. Conclusions: The prevalence of last year asthma symptoms increased compared with a previous study.

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Circadian rhythms govern many aspects of mammalian physiology. The daily pattern of melatonin synthesis and secretion is one of the classic examples of circadian oscillations. It is mediated by a class of neuroendocrine cells known as pinealocytes which are not yet fully defined. An established method to evaluate functional and cytological characters is through the expression of lineage-specific transcriptional regulators. NeuroD1 is a basic helix-loop-helix transcription factor involved in the specification and maintenance of both endocrine and neuronal phenotypes. We have previously described developmental and adult regulation of NeuroD1 mRNA in the rodent pineal gland. However, the transcript levels were not influenced by the elimination of sympathetic input, suggesting that any rhythmicity of NeuroD1 might be found downstream of transcription. Here, we describe NeuroD1 protein expression and cellular localization in the rat pineal gland during development and the daily cycle. In embryonic and perinatal stages, protein expression follows the mRNA pattern and is predominantly nuclear. Thereafter, NeuroD1 is mostly found in pinealocyte nuclei in the early part of the night and in cytoplasm during the day, a rhythm maintained into adulthood. Additionally, nocturnal nuclear NeuroD1 levels are reduced after sympathetic disruption, an effect mimicked by the in vivo administration of α- and ß-adrenoceptor blockers. NeuroD1 phosphorylation at two sites, Ser(274) and Ser(336) , associates with nuclear localization in pinealocytes. These data suggest that NeuroD1 influences pineal phenotype both during development and adulthood, in an autonomic and phosphorylation-dependent manner.

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Casi 500 millones de personas viven dentro de los límites de exposición de los volcanes activos. En junio de 2011, el complejo volcánico Puyehue-Cordón Caulle, situado en el norte de la Patagonia chilena, comenzó un ciclo eruptivo emitiendo un enorme volumen de cenizas. Los vientos dispersaron este material hacia el SE afectando a la ciudad de San Carlos de Bariloche, Argentina. El estudio de cohortes CESCAS y su rama respiratoria, PRISA (Pulmonary Risk in South America Study), se estaba realizando en esa ciudad. Se utilizaron los datos del estudio PRISA para tratar de responder a la pregunta de si la presencia de ceniza volcánica afectó la función respiratoria de los residentes de Bariloche. Tomamos muestras de 767 pruebas de función pulmonar durante los tres meses anteriores (n = 297) y seis meses después (n = 470) de la erupción volcánica. Los participantes no eran los mismos antes y después de la exposición, pero pertenecían a la muestra originalmente seleccionada e incluida en el estudio PRISA. El objetivo fue evaluar si la exposición a la ceniza volcánica se asoció a alteraciones en la función pulmonar evaluada por espirometría. No se encontraron diferencias en FEV1 pre-broncodilatador (p = 0,30), FEV1 post-broncodilatador (p = 0,19), FVC pre-broncodilatador (p = 0,51) o FVC post-broncodilatador (p = 0,26) entre los grupos no expuestos y expuestos. Tampoco hubieron diferencias en la tasa de respuesta a broncodilatador (p = 0,87) o en el subgrupo de asma y EPOC. La exposición a la ceniza volcánica no se asoció con ningún efecto sobre la función respiratoria en una cohorte representativa de la población de San Carlos de Bariloche.

Almost 500 million people live within the exposure range of active volcanoes. In June 2011, the Puyehue-Cordón Caulle Volcanic Complex, located in northern Chilean Patagonia, began an eruptive cycle emitting an enormous volume of ash. Winds dispersed this material toward the SE, affecting the city of San Carlos de Bariloche, Argentina. The CESCAS cohort study and its respiratory branch, PRISA (Pulmonary Risk in South America Study), was underway in that city. We used data from the CESCAS/PRISA study to attempt to answer the question of whether the presence of volcanic ash affected the respiratory function of the residents of Bariloche.This study is nested within the CESCAS/ PRISA study. We sampled 767 pulmonary function tests carried out within three months before (n = 297) and six months after (n = 470) the volcanic eruption. Participants were not the same before and after exposure, but belonged to the original sample included in the PRISA study. The objective was to evaluate whether exposure to volcanic ash was associated to impaired lung function assessed by spirometry. No differences were found in the pre-bronchodilator FEV1 (p = 0.30), post bronchodilator FEV1 (p=0.19), pre-bronchodilator FVC (p=0.51) or post-bronchodilator FVC (p = 0.26) between the non-exposed and exposed group, nor in the rate of bronchodilator responsiveness (p = 0.87)or in the asthmatic and COPD subgroup. Exposure to volcanic ash was not associated to any effect on respiratory function in a representative cohort from the population of San Carlos de Bariloche.

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Apoptosis is necessary for the regulation of growth during development, but the precise details of this regulation have not been completely characterized. In this study, we used the Drosophila genital disc as a model to analyze the contribution of apoptosis to growth regulation. We studied the expression or activity of several elements of the apoptotic death pathway such as Drosophila inhibitor of apoptosis1, caspases, the apoptotic genes reaper (rpr) and head involution defective, as well as elements of the Jun-NH2-terminal kinase (JNK) pathway. We found that the JNK pathway is active in a dynamic, asymmetric and genitalia-specific manner. Apoptosis, as measured in terms of the expression of a variety of apoptotic molecules, occurs in a JNK-dependent and -independent manner and was detected among engrailed (en) expressing cells. JNK regulation of apoptotic genes is necessary to control growth in both sexes and rotation in males; this regulatory role is necessary to execute en(+) cell death and to activate expression of rpr in these cells. rpr is up-regulated at antero-posterior borders, and this expression appears to be of particular importance in the control of growth, since the balance between cell proliferation and death in those regions appears to depend on the equilibrium between pro- and anti-apoptotic factors at a cellular level.

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A través del análisis citogenético se diagnosticaron como freemartin cinco individuos seleccionados de un total de 10 bovinos (Bos taurus) que tenían el antecedente de proceder de partos múltiples heterosexuales; asimismo, se estudiaron anatomopatológicamente dos de estos individuos. La presencia de quimerismo cromosómico (60,XX/60,XY) caracterizó a los animales estudiados, excepcionalmente un individuo freemartin mostró tan sólo células 60,XY, en tanto que los hallazgos anatomopatológicos de dos freemartin estudiados hasta su sacrificio exhibieron masculinización del tracto reproductor con únicamente tejido testicular en las gónadas.

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