An upgrade on the rabbit model of anthracycline-induced cardiomyopathy: shorter protocol, reduced mortality, and higher incidence of overt dilated cardiomyopathy

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality.

Interdecadal changes on the seasonal prediction of the western North Pacific summer climate around the late 1970s and early 1990s

Identifying predictability and the corresponding sources for the western North Pacific (WNP) summer climate in the case of non-stationary teleconnections during recent decades benefits for further improvements of long-range prediction on the WNP and East Asian summers. In the past few decades, pronounced increases on the summer sea surface temperature (SST) and associated interannual variability are observed over the tropical Indian Ocean and eastern Pacific around the late 1970s and over the Maritime Continent and western–central Pacific around the early 1990s. These increases are associated with significant enhancements of the interannual variability for the lower-tropospheric wind over the WNP. In this study, we further assess interdecadal changes on the seasonal prediction of the WNP summer anomalies, using May-start retrospective forecasts from the ENSEMBLES multi-model project in the period 1960–2005. It is found that prediction of the WNP summer anomalies exhibits an interdecadal shift with higher prediction skills since the late 1970s, particularly after the early 1990s. Improvements of the prediction skills for SSTs after the late 1970s are mainly found around tropical Indian Ocean and the WNP. The better prediction of the WNP after the late 1970s may arise mainly from the improvement of the SST prediction around the tropical eastern Indian Ocean. The close teleconnections between the tropical eastern Indian Ocean and WNP summer variability work both in the model predictions and observations. After the early 1990s, on the other hand, the improvements are detected mainly around the South China Sea and Philippines for the lower-tropospheric zonal wind and precipitation anomalies, associating with a better description of the SST anomalies around the Maritime Continent. A dipole SST pattern over the Maritime Continent and the central equatorial Pacific Ocean is closely related to the WNP summer anomalies after the early 1990s. This teleconnection mode is quite predictable, which is realistically reproduced by the models, presenting more predictable signals to the WNP summer climate after the early 1990s.

A low mortality, high morbidity reduced intensity status epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles.

Evaluation of moisture sources for the Central European summer flood of May/June 2013 based on regional climate model simulations

Heavy precipitation affected Central Europe in May/June 2013, triggering damaging floods both on the Danube and the Elbe rivers. Based on a modelling approach with COSMO-CLM, moisture fluxes, backward trajectories, cyclone tracks and precipitation fields are evaluated for the relevant time period 30 May–2 June 2013. We identify potential moisture sources and quantify their contribution to the flood event focusing on the Danube basin through sensitivity experiments: Control simulations are performed with undisturbed ERA-Interim boundary conditions, while multiple sensitivity experiments are driven with modified evaporation characteristics over selected marine and land areas. Two relevant cyclones are identified both in reanalysis and in our simulations, which moved counter-clockwise in a retrograde path from Southeastern Europe over Eastern Europe towards the northern slopes of the Alps. The control simulations represent the synoptic evolution of the event reasonably well. The evolution of the precipitation event in the control simulations shows some differences in terms of its spatial and temporal characteristics compared to observations. The main precipitation event can be separated into two phases concerning the moisture sources. Our modelling results provide evidence that the two main sources contributing to the event were the continental evapotranspiration (moisture recycling; both phases) and the North Atlantic Ocean (first phase only). The Mediterranean Sea played only a minor role as a moisture source. This study confirms the importance of continental moisture recycling for heavy precipitation events over Central Europe during the summer half year.

Seasonality of westerly moisture transport in the East Asian summer monsoon and its implications for interpreting precipitation δ18O

East Asian summer monsoon (EASM) rainfall impacts the world's most populous regions. Accurate EASM rainfall prediction necessitates robust paleoclimate reconstructions from proxy data and quantitative linkage to modern climatic conditions. Many precisely dated oxygen isotope records from Chinese stalagmites have been interpreted as directly reflecting past EASM rainfall amount variability, but recent research suggests that such records instead integrate multiple hydroclimatic processes. Using a Lagrangian precipitation moisture source diagnostic, we demonstrate that EASM rainfall is primarily derived from the Indian Ocean. Conversely, Pacific Ocean moisture export peaks during winter, and the moisture uptake area does not differ significantly between summer and winter and is thus a minor contributor to monsoonal precipitation. Our results are substantiated by an accurate reproduction of summer and winter spatial rainfall distributions across China. We also correlate modern EASM rainfall oxygen isotope ratios with instrumental rainfall amount and our moisture source data. This analysis reveals that the strength of the source effect is geographically variable, and differences in atmospheric moisture transport may significantly impact the isotopic signature of EASM rainfall at the Hulu, Dongge, and Wanxiang Cave sites. These results improve our ability to isolate the rainfall amount signal in paleomonsoon reconstructions and indicate that precipitation across central and eastern China will directly respond to variability in Indian Ocean moisture supply.

Different strategies for improving summer thermal comfort in heavyweight traditional buildings

In order to exploit the passive energy potential of the building envelope, it is important to provide a right combination of insulation thickness, heat capacity and night-time ventilation. In this paper, this issue will be tackled with reference to an historic building in Catania (Southern Italy). The building was built at the end of the XIX century, and its opaque envelope is entirely made with lava stones, which is typical of traditional architecture in this area. Starting from the current configuration of the building, many hypotheses for refurbishment are considered, combined with different strategies for passive cooling, such as night-time ventilation, use of shading devices and adoption of highly-reflective coatings. The effectiveness of each solution in terms of summer thermal comfort is evaluated through dynamic thermal simulations carried out with EnergyPlus. The results show the synergic effect of these strategies, as well as their individual impact, and allow to draw some general conclusions about the behaviour of heavyweight buildings under moderately hot weather conditions.

Understanding the rapid summer warming and changes in temperature extremes since the mid-1990s over Western Europe

Analysis of observations indicates that there was a rapid increase in summer (June-August, JJA) mean surface air temperature (SAT) since the mid-1990s over Western Europe. Accompanying this rapid warming are significant increases in summer mean daily maximum temperature, daily minimum temperature, annual hottest day temperature and warmest night temperature, and an increase in frequency of summer days and tropical nights, while the change in the diurnal temperature range (DTR) is small. This study focuses on understanding causes of the rapid summer warming and associated temperature extreme changes. A set of experiments using the atmospheric component of the state-of-the-art HadGEM3 global climate model have been carried out to quantify relative roles of changes in sea surface temperature (SST)/sea ice extent (SIE), anthropogenic greenhouse gases (GHGs), and anthropogenic aerosols (AAer). Results indicate that the model forced by changes in all forcings reproduces many of the observed changes since the mid-1990s over Western Europe. Changes in SST/SIE explain 62.2% ± 13.0% of the area averaged seasonal mean warming signal over Western Europe, with the remaining 37.8% ± 13.6% of the warming explained by the direct impact of changes in GHGs and AAer. Results further indicate that the direct impact of the reduction of AAer precursor emissions over Europe, mainly through aerosol-radiation interaction with additional contributions from aerosol-cloud interaction and coupled atmosphere-land surface feedbacks, is a key factor for increases in annual hottest day temperature and in frequency of summer days. It explains 45.5% ± 17.6% and 40.9% ± 18.4% of area averaged signals for these temperature extremes. The direct impact of the reduction of AAer precursor emissions over Europe acts to increase DTR locally, but the change in DTR is countered by the direct impact of GHGs forcing. In the next few decades, greenhouse gas concentrations will continue to rise and AAer precursor emissions over Europe and North America will continue to decline. Our results suggest that the changes in summer seasonal mean SAT and temperature extremes over Western Europe since the mid-1990s are most likely to be sustained or amplified in the near term, unless other factors intervene.

Seasonal patterns of viral and bacterial infections among children hospitalized with community-acquired pneumonia in a tropical region

Community-acquired pneumonia (CAP) is a common cause of morbidity among children. Evidence on seasonality, especially on the frequency of viral and bacterial causative agents is scarce; such information may be useful in an era of changing climate conditions worldwide. To analyze the frequency of distinct infections, meteorological indicators and seasons in children hospitalized for CAP in Salvador, Brazil, nasopharyngeal aspirate and blood were collected from 184 patients aged < 5 y over a 21-month period. Fourteen microbes were investigated and 144 (78%) cases had the aetiology established. Significant differences were found in air temperature between spring and summer (p = 0.02) or winter (p < 0.001), summer and fall (p = 0.007) or winter (p < 0.001), fall and winter (p = 0.002), and on precipitation between spring and fall (p = 0.01). Correlations were found between: overall viral infections and relative humidity (p = 0.006; r = 0.6) or precipitation (p = 0.03; r = 0.5), parainfluenza and precipitation (p = 0.02; r = -0.5), respiratory syncytial virus (RSV) and air temperature (p = 0.048; r = -0.4) or precipitation (p = 0.045; r = 0.4), adenovirus and precipitation (p = 0.02; r = 0.5), pneumococcus and air temperature (p = 0.04; r = -0.4), and Chlamydia trachomatis and relative humidity (p = 0.02; r = -0.5). The frequency of parainfluenza infection was highest during spring (32.1%; p = 0.005) and that of RSV infection was highest in the fall (36.4%; p < 0.001). Correlations at regular strength were found between several microbes and meteorological indicators. Parainfluenza and RSV presented marked seasonal patterns.

Trends in systemic lupus erythematosus mortality rates in the state of Sao Paulo, Brazil from 1985 to 2004

Objectives To estimate mortality rates and mortality trends from SLE in the state of Sao Paulo, Brazil. Material and methods The official data bank was used to study all deaths occurred from 1985 to 2004 in which SLE was mentioned as the underlying cause of death. Besides the overall mortality rate, the annual gender- and age-specific mortality rates were estimated for each calendar year by age bracket (0-19 years, 20-39 years, 40-59 years and over 60 years) and for the sub-periods 1985-1995 (first) and 1996-2004 (second), by decades. Chi-square test was used to compare the mortality rates between the two periods, as well the mortality rates according to educational level considering years of study. Pearson correlation coefficient test was used to analyse mortality trends. The crude rates were adjusted for age by the direct method, using the standard Brazilian population in 2000. Results A total of 2,601 deaths (90% female) attributed to SLE were analysed. The mean age at death was significantly higher in the second than in the first sub-period (36.6 +/- 15.6 years vs. 33.9 +/- 14.0 years; p<0.001). The overall adjusted mortality rate was 3.8 deaths/million habitants/year for the entire period and 3.4 deaths/million inhabitants/year for the first and 4.0 deaths/million inhabitants/year for the second sub-period (p<0.001). In each calendar year, the mortality rate was significantly lower for the better educated group. Throughout the period, there was a significant increase in mortality rates only among women over 40. Conclusion SLE patients living in the state of Silo Paulo still die at younger ages than those living in developed countries. Our data do not support the theory that there was an improvement in the SLE mortality rate in the last 20 years in the state of Sao Paulo. Socio-economic factors, such as the difficulty to get medical care and adequate treatment, may be the main factors to explain the worst prognosis for our patients.

Chagas disease-related mortality trends, state of Sao Paulo, Brazil, 1985 to 2006: a study using multiple causes of death

Objectives. To study mortality trends related to Chagas disease taking into account all mentions of this cause listed on any line or part of the death certificate. Methods. Mortality data for 1985-2006 were obtained from the multiple cause-of-death database maintained by the Sao Paulo State Data Analysis System (SEADE). Chagas disease was classified as the underlying cause-of-death or as an associated cause-of-death (non-underlying). The total number of times Chagas disease was mentioned on the death certificates was also considered. Results. During this 22-year period, there were 40 002 deaths related to Chagas disease: 34 917 (87.29%) classified as the underlying cause-of-death and 5 085 (12.71%) as an associated cause-of-death. The results show a 56.07% decline in the death rate due to Chagas disease as the underlying cause and a stabilized rate as associated cause. The number of deaths was 44.5% higher among men. The fact that 83.5% of the deaths occurred after 45 years of age reflects a cohort effect. The main causes associated with Chagas disease as the underlying cause-of-death were direct complications due to cardiac involvement, such as conduction disorders, arrhythmias and heart failure. Ischemic heart disease, cerebrovascular disorders and neoplasms were the main underlying causes when Chagas was an associated cause-of-death. Conclusions. For the total mentions to Chagas disease, a 51.34% decline in the death rate was observed, whereas the decline in the number of deaths was only 5.91%, being lower among women and showing a shift of deaths to older age brackets. Using the multiple cause-of-death method contributed to the understanding of the natural history of Chagas disease.

Sex and socioeconomic inequalities of lung cancer mortality in Barcelona, Spain and Sao Paulo, Brazil

The objective of this paper was to assess sex and socioeconomic inequalities in lung cancer mortality in two major cities of Europe and South America. Official information on mortality and population allowed the estimation of sex- and age-specific death rates for Barcelona, Spain and Sao Paulo, Brazil (1995-2003). Mortality trends and levels were independently assessed for each city and subsequently compared. Rate ratios assessed by Poisson regression analysis addressed hypotheses of association between the outcome and socioeconomic covariates (human development index, unemployment and schooling) at the inner-city area level. Barcelona had a higher mortality in men (76.9/100000 inhabitants) than Sao Paulo (38.2/100 000 inhabitants); although rates were decreasing for the former (-2%/year) and levelled-off for the [after. Mortality in women ranked similarly (9.1 for Barcelona, 11.5 for Sao Paulo); with an increasing trend for women aged 35-64 years (+ 7.7%/year in Barcelona and + 2.4%/year in Sao Paulo). The socioeconomic gradient of mortality in men was negative for Barcelona and positive for Sao Paulo; for women, the socioeconomic gradient was positive in both cities. Negative gradients indicate that deprived areas suffer a higher burden of disease; positive gradients suggest that prosmoking lifestyles may have been more prevalent in more affluent areas during the last decades. Sex and socioeconomic inequalities of lung cancer mortality reinforce the hypothesis that the epidemiologic profile of cancer can be improved by an expanded access to existing technology of healthcare and prevention. The continuous monitoring of inequalities in health may contribute to the concurrent promotion of well-being and social justice.

Paracoccidioidomycosis-related mortality trend, state of Sao Paulo, Brazil: a study using multiple causes of death

Objective. To investigate mortality in which paracoccidioidomycosis appears on any line or part of the death certificate. Method. Mortality data for 1985-2005 were obtained from the multiple cause-of-death database maintained by the Sao Paulo State Data Analysis System (SEADE). Standardized mortality coefficients were calculated for paracoccidioidomycosis as the underlying cause-of-death and as an associated cause-of-death, as well as for the total number of times paracoccidioidomycosis was mentioned on the death certificates. Results. During this 21-year period, there were 1950 deaths related to paracoccidioidomycosis; the disease was the underlying cause-of-death in 1 164 cases (59.69%) and an associated cause-of-death in 786 (40.31%). Between 1985 and 2005 records show a 59.8% decline in the mortality coefficient due to paracoccidioidomycosis as the underlying cause and a 53.0% decline in the mortality as associated cause. The largest number of deaths occurred among men, in the older age groups, and among rural workers, with an upward trend in winter months. The main causes associated with paracoccidioidomycosis as the underlying cause-of-death were pulmonary fibrosis, chronic lower respiratory tract diseases, and pneumonias. Malignant neoplasms and AIDS were the main underlying causes when paracoccidioidomycosis was an associated cause-of-death. The decision tables had to be adapted for the automated processing of causes of death in death certificates where paracoccidioidomycosis was mentioned. Conclusions. Using the multiple cause-of-death method together with the traditional underlying cause-of-death approach provides a new angle on research aimed at broadening our understanding of the natural history of paracoccidioidomycosis.

Subclinical thyroid dysfunctions are independent risk factors for mortality in a 7.5-year follow-up: the Japanese-Brazilian thyroid study

Objective: The currently available data concerning the influence of subclinical thyroid disease (STD) on morbidity and mortality are conflicting. Our objective was to investigate the relationships between STD and cardiometabolic profile and cardiovascular disease at baseline, as well as with all-cause and cardiovascular mortality in a 7.5-year follow-up. Design: Prospective, observational study. Methods: An overall of 1110 Japanese-Brazilians aged above 30 years, free of thyroid disease, and not taking thyroid medication at baseline were studied. In a cross-sectional analysis, we investigated the prevalence of STD and its relationship with cardiometabolic profile and cardiovascular disease. All-cause and cardiovascular mortality rates were assessed for participants followed for up to 7.5 years. Association between STD and mortality was drawn using multivariate analysis, adjusting for potential confounders. Results: A total of 913 (82.3%) participants had euthyroidism, 99 (8.7%) had subclinical hypothyroidism, and 69 (6.2%) had subclinical hyperthyroidism. At baseline, no association was found between STD and cardiometabolic profile or cardiovascular disease. Multivariate-adjusted hazard ratios (HRs (95% confidence interval)) for all-cause mortality were significantly higher for individuals with both subclinical hyperthyroidism (HR, 3.0 (1.5-5.9); n=14) and subclinical hypothyroidism (HR, 2.3 (1.2-4.4); n=13) than for euthyroid subjects. Cardiovascular mortality was significantly associated with subclinical hyperthyroidism (HR, 3.3 (1.4-7.5); n=8), but not with subclinical hypothyroidism (HR, 1.6 (0.6-4.2); n=5). Conclusion: In the Japanese-Brazilian population, subclinical hyperthyroidism is an independent risk factor for all-cause and cardiovascular mortality, while subclinical hypothyroidism is associated with all-cause mortality.

Long-range ozone transport and its impact on respiratory and cardiovascular health in the north of Portugal

Ozone dynamics depend on meteorological characteristics such as wind, radiation, sunshine, air temperature and precipitation. The aim of this study was to determine ozone trajectories along the northern coast of Portugal during the summer months of 2005, when there was a spate of forest fires in the region, evaluating their impact on respiratory and cardiovascular health in the greater metropolitan area of Porto. We investigated the following diseases, as coded in the ninth revision of the International Classification of Diseases: hypertensive disease (codes 401-405); ischemic heart disease (codes 410-414); other cardiac diseases, including heart failure (codes 426-428); chronic obstructive pulmonary disease and allied conditions, including bronchitis and asthma (codes 490-496); and pneumoconiosis and other lung diseases due to external agents (codes 500-507). We evaluated ozone data from air quality monitoring stations in the study area, together with data collected through HYbrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model analysis of air mass circulation and synoptic-scale zonal wind from National Centers for Environmental Prediction data. High ozone levels in rural areas were attributed to the dispersion of pollutants induced by local circulation, as well as by mesoscale and synoptic scale processes. The fires of 2005 increased the levels of pollutants resulting from the direct emission of gases and particles into the atmosphere, especially when there were incoming frontal systems. For the meteorological case studies analyzed, peaks in ozone concentration were positively associated with higher rates of hospital admissions for cardiovascular diseases, although there were no significant associations between ozone peaks and admissions for respiratory diseases.