The underappreciated diversity of bile acid modifications.

The repertoire of modifications to bile acids and related steroidal lipids by host and microbial metabolism remains incompletely characterized. To address this knowledge gap, we created a reusable resource of tandem mass spectrometry (MS/MS) spectra by filtering 1.2 billion publicly available MS/MS spectra for bile-acid-selective ion patterns. Thousands of modifications are distributed throughout animal and human bodies as well as microbial cultures. We employed this MS/MS library to identify polyamine bile amidates, prevalent in carnivores. They are present in humans, and their levels alter with a diet change from a Mediterranean to a typical American diet. This work highlights the existence of many more bile acid modifications than previously recognized and the value of leveraging public large-scale untargeted metabolomics data to discover metabolites. The availability of a modification-centric bile acid MS/MS library will inform future studies investigating bile acid roles in health and disease.

Assessing the socio-economic and land-cover drivers of wildfire activity and its spatiotemporal distribution in south-central Chile.

Sustained human pressures on the environment have significantly increased the frequency, extent, and severity of wildfires, globally. This is particularly the case in Mediterranean regions, in which human-caused wildfires represent up to 90% of all recorded wildfire ignitions. In Chile, it has been estimated that nearly 90% of wildfires are related to human activities, and that their frequency and distribution have steadily increased over the last decade. Despite this, the role of socio-economic factors in driving wildfire activity and its spatiotemporal distribution remains unclear. In this study, we assess the association between socio-economic drivers and spatiotemporal patterns of wildfires in the Mediterranean region of south-central Chile over the period 2010-2018. Our results show that 98.5% of wildfires are related to human activities, either accidentally (58.2%) or intentionally (36.6%). Wildfires occurred primarily during the summer months and their density at the commune-level was associated with increased road access, as well as with the percentage of land covered by agriculture, exotic tree plantations, and native forest. Wildfire activity at the commune-level was also related to socio-economic variables such as population density, proportion of indigenous population, and unemployment rate, although such associations varied considerably depending on the region and on whether the wildfire was started accidentally or intentionally. Our study provides a comprehensive and interdisciplinary assessment of the complex ways in which land-cover and socio-economic factors drive the distribution of wildfire activity in south-central Chile. It represents an important guide for policy-making, as well a baseline for research into strategies aimed at predicting and mitigating wildfire activity at both local and national levels.

Decreased serotonin content and release in the ventral hippocampus of prenatally stressed male rats in response to forced swim test.

Prenatal stress modifies the serotonergic system by altering the synthesis, metabolism, receptors and serotonin content in the hippocampus. However, it is currently unknown whether serotonin release in the ventral hippocampus of prenatally stressed rats is altered. In this study, serotonin (5-HT) and its metabolite, 5­hydroxyindoleacetic acid (5-HIAA) levels were analysed in dialysates (in vivo) and in homogenates (in vitro) of the ventral hippocampus. This was made after the sucrose preference test and after forced swim test (FST) in male adult progeny from mothers that were stressed by immersion in cold water during the last week of gestation. Serum concentration of corticosterone was also evaluated in control and in prenatally stressed males. Sucrose preference was differently affected in prenatally stressed males: 69% showed decreased sucrose consumption, and were considered anhedonic; 31% exhibited sucrose consumption similar to control and were considered non­anhedonic. During the FST, increased immobility and decreased swimming were observed in prenatally stressed males. After sucrose test, content and release of 5­HT in prenatally stressed rats were similar to those in the control group, with higher metabolite. After the FST, 5-HT content increased, but its release increased slightly in anhedonic rats and did not change in non-anhedonic rats, with lower metabolite. The response of the adrenal axis to the FST was larger in anhedonic prenatally stressed males, than in control and non­anhedonic males. These data show that behavioural disruption caused by prenatal stress is related to low release and lower metabolism of serotonin in the ventral hippocampus in adult male offspring, as well as to hyperactivity and hyperreactivity of the adrenal axis.

Serotonin and noradrenaline content and release in the dorsal hippocampus during learning and spatial memory in prenatally stressed rats.

Prenatal stress causes learning and spatial memory deficits in adulthood by modifying hippocampal function. The dorsal hippocampus contains serotonergic and noradrenergic neuron terminals, which are related to cognitive processes. It is currently unknown whether prenatal stress modifies serotonin (5-HT) and noradrenaline (NA) content and their release in the hippocampus during cognitive performance. Therefore, we measured these variables in the dorsal hippocampus of prenatally stressed males during spatial learning and memory tests. Cognitive tests were performed in 3-month-old control and prenatally stressed male rats in the Morris Water Maze (MWM). After cognitive tests, the dorsal hippocampus was dissected to quantify 5-HT and NA content. In other males, 5-HT and NA release in the dorsal hippocampus was assessed by microdialysis, before and after cognitive tests. Prenatally stressed males showed longer latencies to reach the platform, compared to control animals. Hippocampal 5-HT content decreased during learning and memory tasks in both groups, while NA content was not modified in prenatally stressed males neither before, nor after learning and memory tests. 5-HT and NA release were significantly lower in prenatally stressed animals during spatial learning and memory tasks. Corticosterone response was greater in prenatally stressed animals compared to controls. These results show that cognitive disruption caused by prenatal stress is related to decreased 5-HT and NA release, and to higher adrenal axis response in prenatally stressed animals.

Using stated preference methods to design cost-effective subsidy programs to induce technology adoption: an application to a stove program in southern Chile.

We study the design of an economic incentive based program - a subsidy - to induce adoption of more efficient technology in a pollution reduction program in southern Chile. Stated preferences methods, contingent valuation (CV), and choice experiment (CE) are used to estimate the probability of adoption and the willingness to share the cost of a new technology by a household. The cost-effectiveness property of different subsidy schemes is explored numerically for different regulatory objectives. Our results suggest that households are willing to participate in voluntary programs and to contribute by paying a share of the cost of adopting more efficient technologies. We find that attributes of the existing and the new technology, beyond the price, are relevant determinant factors of the participation decision and payment. Limited access to credit markets for low income families can be a major barrier for an effective implementation of these types of programs. Variations in the design of the subsidy and on the regulator's objective and constraints can have significant impact on the level and the cost of reduction of aggregate emissions achieved.

Income-related inequality in health and health care utilization in Chile, 2000-2009.

OBJECTIVE: To measure and explain income-related inequalities in health and health care utilization in the period 2000 - 2009 in Chile, while assessing variations within the country and determinants of inequalities. METHODS: Data from the National Socioeconomic Characterization Survey for 2000, 2003, and 2009 were used to measure inequality in health and health care utilization. Income-related inequality in health care utilization was assessed with standardized concentration indices for the probability and total number of visits to specialized care, generalized care, emergency care, dental care, mental health care, and hospital care. Self-assessed health status and physical limitations were used as proxies for health care need. Standardization was performed with demographic and need variables. The decomposition method was applied to estimate the contribution of each factor used to calculate the concentration index, including ethnicity, employment status, health insurance, and region of residence. RESULTS: In Chile, people in lower-income quintiles report worse health status and more physical limitations than people in higher quintiles. In terms of health service utilization, pro-rich inequities were found for specialized and dental visits with a slight pro-rich utilization for general practitioners and all physician visits. All pro-rich inequities have decreased over time. Emergency room visits and hospitalizations are concentrated among lower-income quintiles and have increased over time. Higher education and private health insurance contribute to a pro-rich inequity in dentist, general practitioner, specialized, and all physician visits. Income contributes to a pro-rich inequity in specialized and dentist visits, whereas urban residence and economic activity contribute to a pro-poor inequity in emergency room visits. CONCLUSIONS: The pattern of health care utilization in Chile is consistent with policies implemented in the country and in the intended direction. The significant income inequality in the use of specialized and dental services, which favor the rich, deserves policy makers' attention and further investigation related to the quality of these services.

Income-related inequality in health and health care utilization in Chile, 2000 - 2009 / Desigualdades en salud y en la atención sanitaria relacionadas con los ingresos en Chile, 2000 - 2009

OBJECTIVE: To measure and explain income-related inequalities in health and health care utilization in the period 2000 - 2009 in Chile, while assessing variations within the country and determinants of inequalities. METHODS: Data from the National Socioeconomic Characterization Survey for 2000, 2003, and 2009 were used to measure inequality in health and health care utilization. Income-related inequality in health care utilization was assessed with standardized concentration indices for the probability and total number of visits to specialized care, generalized care, emergency care, dental care, mental health care, and hospital care. Self-assessed health status and physical limitations were used as proxies for health care need. Standardization was performed with demographic and need variables. The decomposition method was applied to estimate the contribution of each factor used to calculate the concentration index, including ethnicity, employment status, health insurance, and region of residence. RESULTS: In Chile, people in lower-income quintiles report worse health status and more physical limitations than people in higher quintiles. In terms of health service utilization, pro-rich inequities were found for specialized and dental visits with a slight pro-rich utilization for general practitioners and all physician visits. All pro-rich inequities have decreased over time. Emergency room visits and hospitalizations are concentrated among lower-income quintiles and have increased over time. Higher education and private health insurance contribute to a pro-rich inequity in dentist, general practitioner, specialized, and all physician visits. Income contributes to a pro-rich inequity in specialized and dentist visits, whereas urban residence and economic activity contribute to a pro-poor inequity in emergency room visits. CONCLUSIONS: The pattern of health care utilization in Chile is consistent with policies implemented in the country and in the intended direction. The significant income inequality in the use of specialized and dental services, which favor the rich, deserves policy makers' attention and further investigation related to the quality of these services.

OBJETIVO: Medir y explicar las desigualdades en salud y en la utilización de la atención sanitaria relacionadas con los ingresos en Chile durante el período 2000 - 2009, evaluar sus factores determinantes y las variaciones dentro del país. MÉTODOS: Se usaron datos de las Encuestas de Caracterización Nacional Socio-económica de 2000, 2003 y 2009. La desigualdad en la utilización de la atención sanitaria relacionada con los ingresos se evaluó con los índices estandarizados de concentración para la probabilidad y el total de consultas de atención especializada, general, de urgencia, odontológica, de salud mental y hospitalaria. El estado de salud autoevaluado y las limitaciones físicas se usaron como mediciones indirectas de la necesidad de atención sanitaria. Se estandarizó por variables demográficas y de necesidad; se utilizó el método de descomposición para calcular la contribución de cada uno de los factores usados para calcular el índice de concentración, entre ellos la etnia, el estado de empleo, el seguro de salud y la región de residencia. RESULTADOS: Las personas en los quintiles de menores ingresos refirieron peor estado de salud y más limitaciones físicas que las de los quintiles superiores. Se encontraron desigualdades a favor de las personas de mayores ingresos para las consultas especializadas y odontológicas, y una leve utilización mayor en este grupo de consultas generales y totales, aunque todas han disminuido en el tiempo. La atención en salas de emergencias y las hospitalizaciones se concentraron en los quintiles de menores ingresos y han aumentado en el tiempo. Los ingresos y tener mayor educación y seguro de salud privado contribuyen a la inequidad a favor de las personas de mayores ingresos respecto de las consultas odontológicas, generales, especializadas y totales, mientras la residencia urbana y la actividad económica contribuyen a la inequidad a favor de las personas de menores ingresos respecto de las consultas en salas de emergencias. CONCLUSIONES: Los patrones de utilización de la atención sanitaria en Chile concuerdan con las políticas del país y van en la dirección esperada. La significativa desigualdad en el ingreso y en el uso de servicios odontológicos y especializados, que favorece a las personas de mayores ingresos, requiere la atención de las instancias normativas y merece investigaciones adicionales relacionadas con la calidad de estos servicios.

Health equity in an unequal country: the use of medical services in Chile.

INTRODUCTION: A recent health reform was implemented in Chile (the AUGE reform) with the objective of reducing the socioeconomic gaps to access healthcare. This reform did not seek to eliminate the private insurance system, which coexists with the public one, but to ensure minimum conditions of access to the entire population, at a reasonable cost and with a quality guarantee, to cover an important group of health conditions. This paper's main objective is to enquire what has happened with the use of several healthcare services after the reform was fully implemented. METHODS: Concentration and Horizontal Inequity indices were estimated for the use of general practitioners, specialists, emergency room visits, laboratory and x-ray exams and hospitalization days. The change in such indices (pre and post-reform) was decomposed, following Zhong (2010). A "mean effect" (how these indices would change if the differential use in healthcare services were evenly distributed) and a "distribution effect" (how these indices would change with no change in average use) were obtained. RESULTS: Changes in concentration indices were mainly due to mean effects for all cases, except for specialists (where "distribution effect" prevailed) and hospitalization days (where none of these effects prevailed over others). This implies that by providing more services across socioeconomic groups, less inequality in the use of services was achieved. On the other hand, changes in horizontal inequity indices were due to distribution effects in the case of GP, ER visits and hospitalization days; and due to mean effect in the case of x-rays. In the first three cases indices reduced their pro-poorness implying that after the reform relatively higher socioeconomic groups used these services more (in relation to their needs). In the case of x-rays, increased use was responsible for improving its horizontal inequity index. CONCLUSIONS: The increase in the average use of healthcare services after the AUGE reform has not always led to improved equity in the use of such services in most services. This indicates that there are still barriers to the equitable use of healthcare services (e.g. insufficient medical human resources, financial barriers, capacity constraints, etc.) that have remained after the reform.

Assessing the benefits and costs of dryland forest restoration in central Chile.

Investment in natural capital restoration is increasing as a response to the widespread ecological degradation of dryland forests. However, finding efficient mechanisms to promote restoration among private landowners is a significant challenge for policy makers with limited financial resources. Furthermore, few attempts have been made to evaluate the costs and benefits of restoration interventions even though this information is relevant to orient decision making. Hence, our goal was to estimate the benefits and costs of dryland forest restoration by means of reforestation with native trees in a study area in central Chile. To determine benefits we applied a Contingent Valuation questionnaire that allowed for the calculation of willingness to pay measures. Restoration costs were calculated based on market prices following existing technical recommendations developed for the study area. The results showed that the restoration project had a negative NPV irrespective of the discount rate applied in the analysis. Thus, the NPV varied between -US$71,000 and -US$258,000. The NPV attained positive results only for negative discount rates (US$15,039 for -2%) and only when the national subsidy available for forest restoration was taken into account. This shows that landowners in Colliguay do not have incentives for carrying out restoration interventions due to a classic market failure: that in which ecosystems are mismanaged because many of their benefits are externalities from the perspective of landowners. Overall, these results stress the need for developing new compensation mechanisms and enhancing those in existence, with the aim of making restoration competitive with other land uses.

TIMPs and MMPs expression in CSF from patients with TSP/HAM.

The tropical spastic paraparesis or human T-cell lymphotropic virus associated myelopathy (TSP/HAM), has been related with an overexpression of matrix metalloproteinases (MMPs), especially MMP-9. Initial studies of reverse zymography with cerebrospinal fluid (CSF) from TSP/HAM patients, and controls showed the presence of TIMPs, endogenous MMP inhibitors. We determined in CSF the levels of TIMPs by immunoanalysis in 25 patients with TSP/HAM, and compared with two groups: controls and patients with acute and subacute inflammatory neurological diseases. We found that TIMP-2, TIMP-3 and TIMP-4 levels were significantly higher than in controls in both TSP/HAM and inflammatory patients, while TIMP-1 was increased only in the inflammatory group. Levels of MMP-3 and MMP-9 from the two groups of patients showed a significant upregulation in CSF. In the CSF of around the 70% of TSP-HAM and inflammatory patients the presence MMP-9 was detected by zymography, but not in controls. MMP-2 was only overexpressed in the acute inflammatory group. The active form of MMP-2 was observed in both groups of patients with a similar high frequency (60%). MMPs overexpressions are independent of the evolution time of the disease in TSP/HAM. The chronic overexpression of these extracelullar matrix proteins detected in CSF of TSP/HAM should be indirectly produced by secreted viral proteins being responsible for the progression of this disease, accounting for the observed differences with acute inflammatory patients. Our results support the existence of an imbalance between MMPs and their endogenous tissue inhibitors, which could be a pathogenic factor in the chronicity of TSP/HAM.

Introducción a una novedosa forma de artrodesis parcial de la muñeca en el tratamiento de la lesión escafolunar avanzada con colapso / Introducction to a novel form of partial arthrodesis of the doll in the treatment of the lesion advanced escafolunar with collapse

Desde que se describen las artrodesis parciales de muñeca se han sumado un sin número de indicaciones que han puesto a prueba las distintas técnicas sin llegar a una que finalmente satisfaga las expectativas del cirujano, las descritas se introducen con detalles personalizados y adaptados al paciente, pero el próposito final es la preservación del movimiento sin dolor y con el mínimo menoscabo de la fuerza de prensión. La lesión escafolunar avanzada con colapso usualmente se presenta asociada a cambios degenerativos de la articulación radioescafoidea y capitolunar. Se presenta pues una serie de casos donde la fusión es realizada a través de la colocación de un tornillo canulado de 4.0 mm, introducido por la base del segundo metacarpiano y guiado bajo intensificador de imágenes hasta el hueso grande y el semilunar

Sustitución del ligamento cruzado anterior con ligamento artificial Lars artroscópicamente asistida / Sustitution anterior cruciate ligament with ligament artificial lars arthroscopic to attend

En un estudio prospectivo, se valoraron 12 pacientes que acudieron a consulta del Hospital Militar Dr. Carlos Arvelo, entre los años 1997-1999, presentando lesión del ligamento cruzado anterior (LCA). Se les realizó reconstrucción del mismo usando el LARS. Todos masculinos con edades entre 21 y 38 años. La causa más frecuente de lesión fue el traumatismo deportivo. Dentro de las lesiones asociadas, el mecanismo medial estuvo implicado en 10 casos (83 por ciento). Al ser evaluados a las 12 semanas el 87,5 por ciento no presentaban dolor, el promedio de la flexión fue de 120º, el 100 por ciento de los pacientes se había reincorporado al trabajo y el 87.5 a las labores deportivas. El promedio de hospitalización fue de 2 días. Las complicaciones observadas fueron neumonía (1 caso), sinovitis (1 caso) e infección superficial de la herida (1 caso). Se concluye que el LARS cumple con las expectativas de estabilidad del paciente con altas demandas físicas

Sistema DHS en fracturas diafisiarias distales del femur / DHS system in distal diaphysaries fractures of the femur

El sistema DHS (Dynamic hip screw) está indicado para fracturas del fémur proximal que se extienden desde el nivel subcapital hasta el trocánter menor, así como en osteotomías. Su aplicación depende del juicio del cirujano y de la situación alrededor de cada paciente en particular. Tal aseveración la hacemos en ocasión de ilustrar en nuestro trabajo la experiencia de el servicio de Cirugía Ortopédica y Traumatología del Hospital Militar "Dr. Carlos Arvelo", en implantar este sistema en fracturas diafisiarias distales del fémur