Sleep-dependent decorrelation of hippocampal spatial representations.

Neuronal ensembles are crucial for episodic memory and spatial mapping. Sleep, particularly non-REM (NREM), is vital for memory consolidation, as it triggers plasticity mechanisms through brain oscillations that reactivate neuronal ensembles. Here, we assessed their role in consolidating hippocampal spatial representations during sleep. We recorded hippocampus activity in rats performing a spatial object-place recognition (OPR) memory task, during encoding and retrieval periods, separated by intervening sleep. Successful OPR retrieval correlated with NREM duration, during which cortical oscillations decreased in power and density as well as neuronal spiking, suggesting global downregulation of network excitability. However, neurons encoding specific spatial locations (i.e., place cells) or objects during OPR showed stronger synchrony with brain oscillations compared to non-encoding neurons, and the stability of spatial representations decreased proportionally with NREM duration. Our findings suggest that NREM sleep may promote flexible remapping in hippocampal ensembles, potentially aiding memory consolidation and adaptation to novel spatial contexts.

Trajectories of Spirometric Patterns, Obstructive and PRISm, in a Population-Based Cohort in Latin America.

Background: Preserved ratio impaired spirometry (PRISm) has been associated with adverse outcomes and increased transition to other spirometric categories over time. We aimed to examine its prevalence, trajectories over time, and outcomes in a population-based sample from Latin America. Methods: Data were obtained from two population-based surveys of adults from three cities in Latin America (PLATINO study), conducted on the same individuals 5-9 years after their baseline examination. We estimated the frequency of PRISm defined by FEV1/FVC≥0.70 with FEV1 <80%, describing their clinical characteristics, longitudinal transition trajectories over time, factors associated with the transition. Results: At baseline, 2942 participants completed post-bronchodilator spirometry, and 2026 at both evaluations. The prevalence of normal spirometry was 78%, GOLD-stage 1 10.6%, GOLD 2-4 6.5%, and PRISm was: 5.0% (95% CI 4.2-5.8). PRISm was associated with less schooling, more reports of physician-diagnosis of COPD, wheezing, dyspnea, missing days at work, having ≥2 exacerbations in the previous year but without accelerated lung function decline. Mortality risk was significantly higher in PRISm (HR 1.97, 95% CI 1.2-3.3) and COPD GOLD 1-4 categories (HR 1.79, 95% CI 1.3-2.4) compared with normal spirometry. PRISm at baseline most frequently transitioned to another category at follow-up (46.5%); 26.7% to normal spirometry and 19.8% to COPD. The best predictors of transition to COPD were closeness of FEV1/FVC to 0.70, older age, current smoking, and a longer FET in the second assessment. Conclusion: PRISm, is a heterogeneous and unstable condition prone to adverse outcomes that require adequate follow-up.

Educación en pacientes adultos mayores sometidos a endoprótesis total de cadera: Un enfoque centrado en las preferencias de los pacientes / Education in older patients undergoing total hip endoprosthesis: An approach focused on patient preferences

Propósito del estudio: Explorar las preferencias educativas de los beneficiarios adultos de las Garantías Explicitas en Salud (GES) sometidos a una cirugía de endoprótesis total de cadera. Material y método: Estudio descriptivo de carácter mixto. Se diseñó una encuesta que exploró las preferencias educativas referentes a cada etapa del proceso quirúrgico de adultos mayores sometidos electivamente a endoprótesis total de cadera en un centro hospitalario universitario. La encuesta se aplicó retrospectivamente de manera telefónica por un encuestador entrenado. El tiempo transcurrido entre la aplicación de la encuesta y la cirugía fue entre 2 y 14 meses. Resultados: Se incluyeron 63 pacientes, cuya edad promedio fue 72,5 años y el 69,8% correspondía al sexo femenino. Con respecto a su previsión de salud el 57,2% era beneficiario de FONASA y el 42,7% de ISAPRE. Las preferencias de información descritas en nuestra muestra con respecto al proceso quirúrgico desde su inicio a fin, señalan a la cirugía propiamente tal (40,4%) y los cuidados post operatorios (29,3%) como los temas de más interés. Los temas de menor interés fueron los relacionados con cuidados preoperatorios (45,2%) y al proceso de hospitalización (31,7%). Los pacientes encuestados valoraron la información entregada previa a su cirugía como adecuada, útil y fácil de entender. Conclusiones: Los adultos mayores sometidos a endoprótesis señalaron la información específica referente a la cirugía y los cuidados post operatorios como los temas educativos de mayor interés. La información estándar entregada por los médicos tratantes fue bien recibida por los pacientes.

Purpose of the study: To explore the educational preferences of adults aged 65 years and older with hip osteoarthritis undergoing total hip replacement (THA). Methods: Mixed descriptive study. A survey was designed to explore the educational preferences regarding each stage of the surgical process in elderly patients undergoing electively THA for osteoarthritis in a university-affiliated hospital. The survey was applied retrospectively and telephonically by a trained interviewer between 2 and 14 months after the surgery.Results: Sixty-three patients were surveyed, whose average age was 72.5 years, and 69.8% corresponded to females. Regarding their health coverage, 57.2% were beneficiaries of FONASA and 42.7% of ISAPRE. The educational preferences described in our sample regarding the surgical process from its beginning to the end indicate that surgery (40.4%) and post-operative care (29.3%) as the most relevant topics. The topics of least interest were preoperative care (45.2%) and information related to hospitalization (31.7%). The surveyed pa-tients rated their treating physician's education as adequate, helpful, and easy to understand before their surgery. Conclusions: Elderly patients undergoing THA indicated that specific surgery and post-operative care information are the most relevant educational topics.

mGluR-dependent plasticity in rodent models of Alzheimer's disease.

Long-term potentiation (LTP) and depression (LTD) are currently the most comprehensive models of synaptic plasticity models to subserve learning and memory. In the CA1 region of the hippocampus LTP and LTD can be induced by the activation of either NMDA receptors or mGluR5 metabotropic glutamate receptors. Alterations in either form of synaptic plasticity, NMDAR-dependent or mGluR-dependent, are attractive candidates to contribute to learning deficits in conditions like Alzheimer's disease (AD) and aging. Research, however, has focused predominantly on NMDAR-dependent forms of LTP and LTD. Here we studied age-associated changes in mGluR-dependent LTP and LTD in the APP/PS1 mouse model of AD and in Octodon degu, a rodent model of aging that exhibits features of AD. At 2 months of age, APP/PS1 mouse exhibited robust mGluR-dependent LTP and LTD that was completely lost by the 8th month of age. The expression of mGluR protein in the hippocampus of APP/PS1 mice was not affected, consistent with previous findings indicating the uncoupling of the plasticity cascade from mGluR5 activation. In O. degu, the average mGluR-LTD magnitude is reduced by half by the 3 rd year of age. In aged O. degu individuals, the reduced mGluR-LTD correlated with reduced performance in a radial arm maze task. Altogether these findings support the idea that the preservation of mGluR-dependent synaptic plasticity is essential for the preservation of learning capacity during aging.

Identifying hotspots of cardiometabolic outcomes based on a Bayesian approach: The example of Chile.

BACKGROUND: There is a need to identify priority zones for cardiometabolic prevention. Disease mapping in countries with high heterogeneity in the geographic distribution of the population is challenging. Our goal was to map the cardiometabolic health and identify hotspots of disease using data from a national health survey. METHODS: Using Chile as a case study, we applied a Bayesian hierarchical modelling. We performed a cross-sectional analysis of the 2009-2010 Chilean Health Survey. Outcomes were diabetes (all types), obesity, hypertension, and high LDL cholesterol. To estimate prevalence, we used individual and aggregated data by province. We identified hotspots defined as prevalence in provinces significantly greater than the national prevalence. Models were adjusted for age, sex, their interaction, and sampling weight. We imputed missing data. We applied a joint outcome modelling approach to capture the association between the four outcomes. RESULTS: We analysed data from 4,780 participants (mean age (SD) 46 (19) years; 60% women). The national prevalence (percentage (95% credible intervals) for diabetes, obesity, hypertension and high LDL cholesterol were 10.9 (4.5, 19.2), 30.0 (17.7, 45.3), 36.4 (16.4, 57.6), and 13.7 (3.4, 32.2) respectively. Prevalence of diabetes was lower in the far south. Prevalence of obesity and hypertension increased from north to far south. Prevalence of high LDL cholesterol was higher in the north and south. A hotspot for diabetes was located in the centre. Hotspots for obesity were mainly situated in the south and far south, for hypertension in the centre, south and far south and for high LDL cholesterol in the far south. CONCLUSIONS: The distribution of cardiometabolic risk factors in Chile has a characteristic pattern with a general trend to a north-south gradient. Our approach is reproducible and demonstrates that the Bayesian approach enables the accurate identification of hotspots and mapping of disease, allowing the identification of areas for cardiometabolic prevention.

PRDM15 Is Associated with Risk of Chronic Obstructive Pulmonary Disease in a Rural Population in Chile.

BACKGROUND: Genome-wide association studies (GWAS) have accelerated our understanding of the genetic underpinnings of chronic obstructive pulmonary disease (COPD); however, GWAS populations have typically consisted of European descent, with ∼1% of Latin American ancestry. OBJECTIVE: To overcome this limitation, we conducted a GWAS in a rural Chilean population with increased COPD risk to investigate genetic variation of COPD risk in this understudied minority population. METHOD: We carried out a case-control study of 214 COPD patients (defined by the GOLD criteria) and 193 healthy controls in Talca, Chile. DNA was extracted from venous blood and genotyped on the Illumina Global Screening Array (n = 754,159 markers). After exclusion based on Hardy-Weinberg equilibrium (p ≤ 0.001), call rates (<95%), and minor allele frequencies (<0.5%) in controls, 455,564 markers were available for logistic regression. RESULTS: PRDM15 rs1054761 C allele (p = 2.22 × 10-7) was associated with decreased COPD risk. Three PRDM15 SNPs located on chromosome 21 were significantly associated with COPD risk (p < 10-6). Two of these SNPs, rs1054761 and rs4075967, were located on a noncoding transcript variant region of the gene. CONCLUSION: PRDM15 overexpression may play a role in the B-cell dysregulation in COPD pathogenesis. To the best of our knowledge, the association between PRDM15 and COPD risk was not previously found in GWAS studies in largely European populations, highlighting the importance of investigating novel variants associated with COPD risk among ethnically diverse populations.

Does educational level predict hearing aid self-efficacy in experienced older adult hearing aid users from Latin America? Validation process of the Spanish version of the MARS-HA questionnaire.

Hearing aids are the most common rehabilitation strategy for age-related hearing loss. However, 25% to 50% of older adults fitted with hearing aids do not wear them post-fitting. Hearing aid self-efficacy has been suggested as one of the key factors that may explain adherence to hearing aids in older adults. The primary aim of this study was to determine a possible association between educational level and hearing aid self-efficacy in older adult hearing aid users from a Latin American country (i.e., Chile). The secondary aim was to determine if in this sample of older adults, hearing aid self-efficacy predicted hearing aid adherence as previously suggested by other studies. The MARS-HA (Measure of Audiologic Rehabilitation Self-Efficacy for Hearing Aids) questionnaire was used to measure hearing aid self-efficacy. This questionnaire was initially adapted into Spanish (S-MARS-HA) using forward and backward translations by bilingual English-Spanish speakers. A sample of 252 older adults fitted with hearing aids at a public hospital in Santiago, Chile, was investigated. Educational level was measured as the number of years of formal education. Participants responded to the S-MARS-HA along with questions exploring social support, attitudes in using hearing aids, participation in social events, and vision and joint problems. Hearing aid adherence was investigated with the use of a question from the International Outcome Inventory for Hearing Aids. All these procedures were conducted at the participants' homes. Pure-tone average (PTA; 500-4000 Hz) in the fitted ear was obtained from the participants' medical records. Univariate and multivariate regression models were constructed to investigate the association between educational level and hearing aid self-efficacy controlling for the covariates of interest (e.g., social support, attitudes in using hearing aids, PTA). The S-MARS-HA showed an adequate construct validity along with a good reliability. Results of the multivariate regression analyses showed that educational level significantly predicted hearing aid self-efficacy. Covariates significantly associated with this outcome included attitudes in using hearing aids and PTA in the fitted ear. Finally, a significant association between hearing aid self-efficacy and adherence to hearing aid use was observed. In conclusion, this study showed a significant association between educational level and hearing aid self-efficacy in older adults from a developing Latin American country. Thus, this variable should be considered when designing and delivering aural rehabilitation programs such as hearing aids to older adults, especially those from developing countries.

Effects of auditory and socio-demographic variables on discontinuation of hearing aid use among older adults with hearing loss fitted in the Chilean public health sector.

BACKGROUND: The percentage of older adults with hearing loss who stop using their hearing aids and the variables associated with this phenomenon have not been systematically investigated in South America. This problem is relevant to the region since countries such as Colombia, Brazil and Chile have public programmes that provide hearing aids to older adults. The aims of this study were to determine the percentage of older adults fitted with a hearing aid at a public hospital in Chile who subsequently stop using it and the auditory and socio-demographic variables associated with the hazard of discontinuing hearing aid use. METHODS: A group that included 355 older adults who had been fitted with a hearing aid was studied retrospectively. In a structured interview, participants were asked about socio-demographic variables and answered part of the Chilean National Survey on Health, evaluating self-perceived hearing loss and responding to questions about discontinuation of hearing aid use and their satisfaction with the device. Survival models were applied to determine the hazard of stopping hearing aid use in relation to the variables of interest. RESULTS: The rate of discontinuation of hearing aid use reached 21.7%. Older adults stopped using their hearing aids mainly during the first 5-6 months post-fitting, and then this number steadily increased. The income fifth quintile was 2.56 times less likely to stop using the hearing aid compared to the first. Those who self-reported that they could not hear correctly without the hearing aid were 2.62 times less likely to stop using it compared to those who reported normal hearing. The group that was very dissatisfied with the hearing aid was 20.86 times more likely to discontinue use than those who reported satisfaction with the device. CONCLUSIONS: Socio-demographic variables such as economic income and auditory factors such as self-perceived hearing loss and satisfaction with the device were significantly associated with the hazard of stopping hearing aid use. Self-perceived hearing loss should be considered part of the candidacy criteria for hearing aids in older adults in Chile and other (developing) countries.

Outcomes for symptomatic non-obstructed individuals and individuals with mild (GOLD stage 1) COPD in a population based cohort.

BACKGROUND: We aimed to study the adverse outcomes of symptomatic and asymptomatic non-obstructed individuals and those with mild COPD longitudinally in participants from three Latin-American cities. METHODS: Two population-based surveys of adults with spirometry were conducted for these same individuals with a 5- to 9-year interval. We evaluated the impact of respiratory symptoms (cough, phlegm, wheezing or dyspnea) in non-obstructed individuals, and among those classified as Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1, COPD on exacerbation frequency, mortality and FEV1 decline, compared with asymptomatic individuals without airflow obstruction or restriction. RESULTS: Non-obstructed symptomatic individuals had a marginal increased risk of mortality (HR 1.3; 95% CI 0.9-1.94), increased FEV1 decline (-4.5 mL/year; 95% CI -8.6, -0.4) and increased risk of 2+ exacerbations in the previous year (OR 2.6; 95% CI 1.2-6.5). Individuals with GOLD stage 1 had a marginal increase in mortality (HR 1.5; 95% CI 0.93-2.3) but a non-significant impact on FEV1 decline or exacerbations compared with non-obstructed individuals. CONCLUSIONS: The presence of respiratory symptoms in non-obstructed individuals was a predictor of mortality, lung-function decline and exacerbations, whereas the impact of GOLD stage 1 was mild and inconsistent. Respiratory symptoms were associated with asthma, current smoking, and the report of heart disease. Spirometric case-finding and treatment should target individuals with moderate-to-severe airflow obstruction and those with restriction, the groups with consistent increased mortality.

Correction to: Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

In the original publication [1] is an error in table 1. The correct version can be found in this Erratum.

Indoor PM2.5 in an urban zone with heavy wood smoke pollution: The case of Temuco, Chile.

Temuco is a mid-size city representative of severe wood smoke pollution in southern Chile; however, little is known about the indoor air quality in this region. A field measurement campaign at 63 households in the Temuco urban area was conducted in winter 2014 and is reported here. In this study, indoor and outdoor (24-hr) PM2.5 and its elemental composition were measured and compared. Infiltration parameters and outdoor/indoor contributions to indoor PM2.5 were also determined. A statistical evaluation of how various air quality interventions and household features influence indoor PM2.5 was also performed. This study determined median indoor and outdoor PM2.5 concentrations of 44.4 and 41.8 µg/m3, respectively. An average infiltration factor (0.62 ±â€¯0.06) was estimated using sulfur as a tracer species. Using a simple mass balance approach, median indoor and outdoor contributions to indoor PM2.5 concentrations were then estimated as 12.5 and 26.5 µg/m3, respectively; therefore, 68% of indoor PM2.5 comes from outdoor infiltration. This high percentage is due to high outdoor pollution and relatively high household air exchange rates (median: 1.06 h-1). This study found that S, Br and Rb were dominated by outdoor contributions, while Si, Ca, Ti, Fe and As originated from indoor sources. Using continuous indoor and outdoor PM2.5 measurements, a median indoor source strength of 75 µg PM2.5/min was estimated for the diurnal period, similar to literature results. For the evening period, the median estimate rose to 135 µg PM2.5/min, reflecting a more intense wood burning associated to cooking and space heating at night. Statistical test results (at the 90% confidence level) support the ongoing woodstove replacement program (reducing emissions) and household weatherization subsidies (reducing heating demand) for improving indoor air quality in southern Chile, and suggest that a cookstove improvement program might be helpful as well.

Comparative analysis of COPD associated with tobacco smoking, biomass smoke exposure or both.

BACKGROUND: Exposure to noxious gases and particles contained in both tobacco smoking (TS) and biomass smoke (BS) are well recognized environmental risk factors for chronic obstructive pulmonary disease (COPD). COPD is characterized by an abnormal inflammatory response, both in the pulmonary and systemic compartments. The differential effects of TS, BS or their combined exposure have not been well characterized yet. This study sought to compare the lung function characteristics and systemic inflammatory response in COPD patients exposed to TS, BS or their combination. METHODS: Sociodemographic, clinical and lung functional parameters were compared across 49 COPD patients with a history of smoking and no BS exposure (TS COPD), 31 never-smoker COPD patients with BS exposure (BS COPD), 46 COPD patients with a combined exposure (TS + BS COPD) and 52 healthy controls (HC) who have never been exposed neither to TS or BS. Blood cell counts, C-reactive protein (CRP), fibrinogen and immunoglobulin E (IgE) levels were quantified in all four groups. RESULTS: TS + BS COPD patients exhibited significantly lower oxygen saturation than the rest of groups (p < 0.01). Spirometry and diffusing capacity were significantly higher in BS than in TS or TS + BS patients. CRP levels were significantly higher in TS COPD patients than in BS COPD group (p < 0.05), whereas fibrinogen was raised in COPD patients with a history of smoking (TS and TS + BS) when compared to control subjects (p < 0.01). Finally, COPD patients with BS exposure (BS and BS + TS groups) showed higher IgE levels than TS and HC (p < 0.05). CONCLUSIONS: There are significant physiological and inflammatory differences between COPD patients with TS, BS and TS + BS exposures. The latter had worse blood oxygenation, whereas the raised levels of IgE in BS exposed patients suggests a differential Th2 systemic inflammatory pattern triggered by this pollutant.

The boundaries of mild chronic obstructive pulmonary disease (COPD): design of the searching clinical COPD onset (SOON) study.

INTRODUCTION: Clinical onset of chronic obstructive pulmonary disease (COPD) is the point at which the disease is first identifiable by physicians. It is a poorly defined stage which seems to include both mild spirometric and non-spirometric disease, and could be described as early grade COPD, for practical purposes. While dyspnoea; chronic bronchitis and CT imaging evidence of emphysema and airway disease may be present very early, the lone significance of dyspnoea, the most relevant symptom in COPD in identifying these individuals, has been scarcely assessed.The Searching Clinical COPD Onset (SOON) Study was designed primarily to detect clinical, physiological and structural differences between dyspnoeic and non-dyspnoeic individuals with early grade COPD. It is hypothesised that presence of dyspnoea in early disease may identify a subtype of individuals with reduced exercise capacity, notwithstanding of their spirometry results. In addition, dyspnoeic individuals will share worse quality of life, lower physical activity, greater lung hyperinflation greater emphysema and airway thickness and reduced peripheral muscle mass than their non-dyspnoeic counterpart. METHODS AND ANALYSIS: SOON is a monocentric study, with a cross sectional design aimed at obtaining representative samples of current or ex-smoker-adults aged ≥45 and ≤80 years. Two hundred and forty participants will be enrolled into four strata, according to normal spirometry or mild spirometric obstruction and presence or not of dyspnoea modified Medical Research Council score ≥1. The primary outcome will be the difference between dyspnoeic and non-dyspnoeic individuals on the 6-min walk test performance, regardless of their spirometry results. To account for the confounding effect of heart failure on dyspnoea, stress echocardiography will be also performed. Secondary outcomes will include clinical (quality of life, physical activity), physiological (exercise testing) and structural characteristics (emphysema, airway disease and peripheral muscle mass by CT imaging). ETHICS AND DISSEMINATION: The Institutional Ethics Committee from Pontificia Universidad Católica de Chile has approved the study protocol and signed informed consent will be obtained from all participants. The findings of the trial will be disseminated through relevant peer-reviewed journals and international conference presentations. TRIAL REGISTRATION NUMBER: NCT03026439.

Prevalence and associated factors of hearing aid use among older adults in Chile.

OBJECTIVE: The aim of this study was to determine the prevalence of use of hearing aids by older adults in Chile and the influence of some variables such as education level, income level and geographic area of residence on the prevalence of hearing aids. DESIGN: A national cross-sectional survey which was carried out in 2009. STUDY SAMPLE: A representative sample of 4766 Chilean older adults aged 60 years and above. RESULTS: The percentage of older adults in Chile who self-reported hearing problems and used hearing aids was 8.9%. Such prevalence increased for adults living in urban areas and for those who knew about the new Chilean programme of universal access to health services (AUGE). For older adults who did not know about this programme, significant associations between the use of hearing aids and the variables of age, geographic area of residence, and income level were found. CONCLUSIONS: People's knowledge about AUGE programme may positively influence the use of hearing aids, although a direct effect cannot be attributed.

The PLATINO study: description of the distribution, stability, and mortality according to the Global Initiative for Chronic Obstructive Lung Disease classification from 2007 to 2017.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) report provides a framework for classifying COPD reflecting the impacts of disease on patients and for targeting treatment recommendations. The GOLD 2017 introduced a new classification with 16 subgroups based on a composite of spirometry and symptoms/exacerbations. METHODS: Data from the population-based PLATINO study, collected at baseline and at follow-up, in three sites in Latin America were analyzed to compare the following: 1) the distribution of COPD patients according to GOLD 2007, 2013, and 2017; 2) the stability of the 2007 and 2013 classifications; and 3) the mortality rate over time stratified by GOLD 2007, 2013, and 2017. RESULTS: Of the 524 COPD patients evaluated, most of them were classified as Grade I or II (GOLD 2007) and Group A or B (GOLD 2013), with ≈70% of those classified as Group A in GOLD 2013 also classified as Grade I in GOLD 2007 and the highest percentage (41%) in Group D (2013) classified as Grade III (2007). According to GOLD 2017, among patients with Grade I airflow limitation, 69% of them were categorized into Group A, whereas Grade IV patients were more evenly distributed among Groups A-D. Most of the patients classified by GOLD 2007 remained in the same airflow limitation group at the follow-up; a greater temporal variability was observed with GOLD 2013 classification. Incidence-mortality rate in patients classified by GOLD 2007 was positively associated with increasing severity of airflow obstruction; for GOLD 2013 and GOLD 2017 (Groups A-D), highest mortality rates were observed in Groups C and D. No clear pattern was observed for mortality across the GOLD 2017 subgroups. CONCLUSION: The PLATINO study data suggest that GOLD 2007 classification shows more stability over time compared with GOLD 2013. No clear patterns with respect to the distribution of patients or incidence-mortality rates were observed according to GOLD 2013/2017 classification.

Lung function decline in subjects with and without COPD in a population-based cohort in Latin-America.

BACKGROUND: Lung-function decline is one of the possible mechanisms leading to Chronic Obstructive Pulmonary Disease (COPD). METHODS: We analyzed data obtained from two population-based surveys of adults (n = 2026) conducted in the same individuals 5-9 years (y) after their baseline examination in three Latin-American cities. Post BronchoDilator (postBD) FEV1 decline in mL/y, as %predicted/y (%P/y) and % of baseline/y (%B/y) was calculated and the influence of age, gender, BMI, baseline lung function, BD response, exacerbations rate evaluated using multivariate models. RESULTS: Expressed in ml/y, the mean annual postBD FEV1 decline was 27 mL (0.22%P, 1.32%B) in patients with baseline COPD and 36 (0.14%P, 1.36%B) in those without. Faster decline (in mL/y) was associated with higher baseline lung function, with significant response to bronchodilators, older age and smoking at baseline, also in women with chronic cough and phlegm, or ≥2 respiratory exacerbations in the previous year, and in men with asthma. CONCLUSIONS: Lung function decline in a population-based cohort did not differ in obstructed and non-obstructed individuals, it was proportional to baseline FEV1, and was higher in smokers, elderly, and women with respiratory symptoms.

Socioeconomic inequalities in alcohol consumption in Chile and Finland.

BACKGROUND: Reasons for socioeconomic inequalities in alcohol harm are not sufficiently understood. One explanation relates to differential exposure to alcohol by socioeconomic status (SES). The present study investigated socioeconomic inequalities in alcohol use in two countries with high alcohol consumption and alcohol harm. METHODS: Data from nationally representative surveys in 2009-2010 in Chile and in 2008-2011 in Finland were used. Surveys comprised 3477 participants in Chile and 9994 in Finland aged 30-64 years. Outcome measures included abstinence, weekly consumption of pure alcohol, heavy volume drinking and heavy episodic drinking (HED). We employed a novel method in alcohol research, the concentration index, to measure socioeconomic inequalities. RESULTS: Alcohol abstinence showed a strong association with lower SES in Chile and Finland. These were largely driven by inequalities among women in Chile and older subgroups in Finland. In both countries, women aged 45-64 of higher SES showed higher weekly consumption of pure alcohol and heavy volume drinking. Heavy volume drinking among Chilean women aged 45-64 showed the highest inequality, favouring higher SES. HED was equally distributed among SES groups in Chile; in Finland HED disproportionally affected lower SES groups. CONCLUSIONS: Lower SES was associated with higher abstinence rates in both countries and heavy episodic drinking in Finland. Heavy volume drinking was more prevalent in middle-aged women of high SES. The results identified groups for targeted interventions, including middle-aged higher SES women, who traditionally have not been specifically targeted. The concentration index could be a useful measure of inequalities in alcohol use.

Laboratory-based and office-based risk scores and charts to predict 10-year risk of cardiovascular disease in 182 countries: a pooled analysis of prospective cohorts and health surveys.

BACKGROUND: Worldwide implementation of risk-based cardiovascular disease (CVD) prevention requires risk prediction tools that are contemporarily recalibrated for the target country and can be used where laboratory measurements are unavailable. We present two cardiovascular risk scores, with and without laboratory-based measurements, and the corresponding risk charts for 182 countries to predict 10-year risk of fatal and non-fatal CVD in adults aged 40-74 years. METHODS: Based on our previous laboratory-based prediction model (Globorisk), we used data from eight prospective studies to estimate coefficients of the risk equations using proportional hazard regressions. The laboratory-based risk score included age, sex, smoking, blood pressure, diabetes, and total cholesterol; in the non-laboratory (office-based) risk score, we replaced diabetes and total cholesterol with BMI. We recalibrated risk scores for each sex and age group in each country using country-specific mean risk factor levels and CVD rates. We used recalibrated risk scores and data from national surveys (using data from adults aged 40-64 years) to estimate the proportion of the population at different levels of CVD risk for ten countries from different world regions as examples of the information the risk scores provide; we applied a risk threshold for high risk of at least 10% for high-income countries (HICs) and at least 20% for low-income and middle-income countries (LMICs) on the basis of national and international guidelines for CVD prevention. We estimated the proportion of men and women who were similarly categorised as high risk or low risk by the two risk scores. FINDINGS: Predicted risks for the same risk factor profile were generally lower in HICs than in LMICs, with the highest risks in countries in central and southeast Asia and eastern Europe, including China and Russia. In HICs, the proportion of people aged 40-64 years at high risk of CVD ranged from 1% for South Korean women to 42% for Czech men (using a ≥10% risk threshold), and in low-income countries ranged from 2% in Uganda (men and women) to 13% in Iranian men (using a ≥20% risk threshold). More than 80% of adults were similarly classified as low or high risk by the laboratory-based and office-based risk scores. However, the office-based model substantially underestimated the risk among patients with diabetes. INTERPRETATION: Our risk charts provide risk assessment tools that are recalibrated for each country and make the estimation of CVD risk possible without using laboratory-based measurements. FUNDING: National Institutes of Health.

Short-term dynamics of indoor and outdoor endotoxin exposure: Case of Santiago, Chile, 2012.

Indoor and outdoor endotoxin in PM2.5 was measured for the very first time in Santiago, Chile, in spring 2012. Average endotoxin concentrations were 0.099 and 0.094 [EU/m(3)] for indoor (N=44) and outdoor (N=41) samples, respectively; the indoor-outdoor correlation (log-transformed concentrations) was low: R=-0.06, 95% CI: (-0.35 to 0.24), likely owing to outdoor spatial variability. A linear regression model explained 68% of variability in outdoor endotoxins, using as predictors elemental carbon (a proxy of traffic emissions), chlorine (a tracer of marine air masses reaching the city) and relative humidity (a modulator of surface emissions of dust, vegetation and garbage debris). In this study, for the first time a potential source contribution function (PSCF) was applied to outdoor endotoxin measurements. Wind trajectory analysis identified upwind agricultural sources as contributors to the short-term, outdoor endotoxin variability. Our results confirm an association between combustion particles from traffic and outdoor endotoxin concentrations. For indoor endotoxins, a predictive model was developed but it only explained 44% of endotoxin variability; the significant predictors were tracers of indoor PM2.5 dust (Si, Ca), number of external windows and number of hours with internal doors open. Results suggest that short-term indoor endotoxin variability may be driven by household dust/garbage production and handling. This would explain the modest predictive performance of published models that use answers to household surveys as predictors. One feasible alternative is to increase the sampling period so that household features would arise as significant predictors of long-term airborne endotoxin levels.

Metabotropic Glutamate Receptors Induce a Form of LTP Controlled by Translation and Arc Signaling in the Hippocampus.

Activity-dependent bidirectional modifications of excitatory synaptic strength are essential for learning and storage on new memories. Research on bidirectional synaptic plasticity has largely focused on long-term potentiation (LTP) and long-term depression (LTD) mechanisms that rely on the activation of NMDA receptors. In principle, metabotropic glutamate receptors (mGluRs) are also suitable to convert synaptic activity into intracellular signals for synaptic modification. Indeed, dysfunction of a form of LTD that depends on Type I mGluRs (mGluR-LTD), but not NMDARs, has been implicated in learning deficits in aging and mouse models of several neurological conditions, including Fragile X syndrome and Alzheimer's disease. To determine whether mGluR activation can also induce LTP in the absence of NMDAR activation, we examined in hippocampal slices from rats and mice, an NMDAR-independent form of LTP previously characterized as dependent on voltage-gated Ca(2+) channels. We found that this form of LTP requires activation of Type I mGluRs and, like mGluR-LTD but unlike NMDAR-dependent plasticity, depends crucially on protein synthesis controlled by fragile X mental retardation protein and on Arc signaling. Based on these observations, we propose the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs. SIGNIFICANCE STATEMENT: Bidirectional changes of synaptic strength are crucial for the encoding of new memories. Currently, the only activity-dependent mechanism known to support such bidirectional changes are long-term potentiation (LTP) and long-term depression (LTD) forms that relay on the activation of NMDA receptors. Metabotropic glutamate receptors (mGluRs) are, in principle, also suitable to trigger bidirectional synaptic modifications. However, only the mGluR-dependent form of LTD has been characterized. Here we report that an NMDAR-independent form of LTP, initially characterized as dependent on voltage-gated Ca(2+) channels, also requires the activation of mGluRs. These finding suggest the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs.