Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle

Brain cells continuously produce and release protons into the extracellular space, with the rate of acid production corresponding to the levels of neuronal activity and metabolism. Efficient buffering and removal of excess H+ is essential for brain function, not least because all the electrogenic and biochemical machinery of synaptic transmission is highly sensitive to changes in pH. Here, we describe an astroglial mechanism that contributes to the protection of the brain milieu from acidification. In vivo and in vitro experiments conducted in rodent models show that at least one third of all astrocytes release bicarbonate to buffer extracellular H+ loads associated with increases in neuronal activity. The underlying signalling mechanism involves activity-dependent release of ATP triggering bicarbonate secretion by astrocytes via activation of metabotropic P2Y1 receptors, recruitment of phospholipase C, release of Ca2+ from the internal stores, and facilitated outward HCO3− transport by the electrogenic sodium bicarbonate cotransporter 1, NBCe1. These results show that astrocytes maintain local brain extracellular pH homeostasis via a neuronal activity-dependent release of bicarbonate. The data provide evidence of another important metabolic housekeeping function of these glial cells

CO2 signaling mediates neurovascular coupling in the cerebral cortex

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3− transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

Promoção, prevenção e cuidado da hipertensão arterial no Brasil

OBJETIVO: Estimar a prevalência de ações de promoção, prevenção e cuidado da hipertensão arterial em adultos e identificar sua associação com estado descompensado de hipertensão. MÉTODOS: Estudo epidemiológico transversal de base populacional realizado por meio de entrevista com 12.324 adultos, de 20 a 59 anos, em 100 municípios brasileiros. As variáveis independentes, consideradas como promoção, prevenção e cuidado, foram: ter recebido orientações sobre a manutenção do peso ideal e sobre atividade física; ter consultado um médico e ter realizado eletrocardiograma no último ano. Pressão arterial acima de 140/90 mmHg foi considerada estado descompensado, sendo a variável dependente para a avaliação da qualidade do cuidado. RESULTADOS: Do total, 16,3% (n = 2.004) referiram diagnóstico médico de hipertensão. As maiores prevalências de hipertensão foram observadas na categoria de idade de 50 a 59 anos, concentradas nas regiões Sudeste e Centro-Oeste. Mais da metade (66,1%) esteve em consulta médica por hipertensão no último ano, da qual metade (52,4%) realizou eletrocardiograma. Dos hipertensos que tiveram sua pressão arterial aferida na entrevista (74,6%), menos da metade (42,4%) apresentava cifras tensionais descompensadas. CONCLUSÕES: Não houve associação entre haver consultado médico no último ano e cifras tensionais descompensadas. A proporção de hipertensos descompensados foi significativamente menor entre os que foram orientados para manter o peso ideal, realizar atividade física e os que fizeram eletrocardiograma. Ser do sexo masculino, ter idade acima de 40 anos e habitar na região Sul mostraram-se associados a estado descompensado da hipertensão.OBJECTIVE: To estimate the prevalence of promotion, prevention and arterial hypertension care actions in adults and to identify their association with decompensated hypertension. METHODS: A population-based cross-sectional epidemiological study was conducted by interviewing 12,324 adults aged from 20 to 59 years, in 100 Brazilian cities. The independent variables considered as promotion, prevention and hypertension care were as follows: to have received guidance on ideal weight maintenance and physical activity practice; to have consulted a doctor; and to have had an electrocardiogram performed in the previous year. A blood pressure higher than 140/90 mm/Hg was considered to be decompensated, being the dependent variable adopted to assess quality of care. RESULTS: Of all participants, 16.3% (n = 2,004) reported a medical diagnosis of hypertension. The highest prevalences of hypertension were observed in the 50 to 59 year age group, primarily in the Southeast and Center-West regions. More than half (66.1%) of participants had a medical consultation about hypertension in the previous year, of which half (52.4%) had an electrocardiogram. Of all those with hypertension who had their blood pressure measured during interview (74.6%), less than half (42.4%) had decompensated values. CONCLUSIONS: There was no association between having consulted a doctor in the previous year and decompensated blood pressure values. The proportion of decompensated hypertensive participants was significantly lower among those who had received guidance on ideal weight maintenance and physical activity practice and those who had had an electrocardiogram performed. The following factors were associated with decompensated hypertension: to be male, to be aged more than 40 years and to live in the South region.OBJETIVO: Estimar la prevalencia de acciones de promoción, prevención y cuidado de la hipertensión arterial en adultos e identificar la asociación con el estado descompensado de hipertensión. MÉTODOS: Estudio epidemiológico transversal de base poblacional realizado a través de entrevista en 12.324 adultos, de 20 a 59 años, en 100 municipios brasileños. Las variables independientes, consideradas como promoción, prevención y cuidado fueron: haber recibido orientaciones sobre la manutención del peso ideal y actividad física; haber consultado un médico y haber realizado el electrocardiograma en el último año. Presión arterial por encima de 140/90 mm/Hg se consideró estado descompensado, siendo la variable dependiente para la evaluación de la calidad del cuidado. RESULTADOS: del total, 16,3% (n= 2.004) refirieron diagnóstico médico de hipertensión. Las mayores prevalencias de hipertensión se observaron en la categoría de edad de 50 a 59 años, concentradas en las regiones Sureste y Centro-Oeste. Más de la mitad (66,1%) estuvo en consulta médica por hipertensión en el último año, y la mitad de estos (52,4%) realizó electrocardiograma. De los hipertensos que chequearon la presión arterial en la entrevista, 74,6%, menos de la mitad (42,4%) presentó cifras tensionales descompensadas. CONCLUSIONES: No hubo asociación entre haber consultado el médico en el último año y cifras tensionales descompensadas. La proporción de hipertensos descompensados fue significativamente menor entre los que fueron orientados para mantener el peso ideal, realizar actividad física y los que hicieron electrocardiograma. Ser del sexo masculino, tener edad por encima de 40 años y habitar en la región Sur, se evidenciaron asociados al estado descompensado de la hipertensión

The development and application of a new tool to assess the adequacy of the content and timing of antenatal care

Abstract Background: Current measures of antenatal care use are limited to initiation of care and number of visits. This study aimed to describe the development and application of a tool to assess the adequacy of the content and timing of antenatal care. Methods: The Content and Timing of care in Pregnancy (CTP) tool was developed based on clinical relevance for ongoing antenatal care and recommendations in national and international guidelines. The tool reflects minimal care recommended in every pregnancy, regardless of parity or risk status. CTP measures timing of initiation of care, content of care (number of blood pressure readings, blood tests and ultrasound scans) and whether the interventions were received at an appropriate time. Antenatal care trajectories for 333 pregnant women were then described using a standard tool (the APNCU index), that measures the quantity of care only, and the new CTP tool. Both tools categorise care into 4 categories, from ‘Inadequate’ (both tools) to ‘Adequate plus’ (APNCU) or ‘Appropriate’ (CTP). Participants recorded the timing and content of their antenatal care prospectively using diaries. Analysis included an examination of similarities and differences in categorisation of care episodes between the tools. Results: According to the CTP tool, the care trajectory of 10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as sufficient and 45,3% as appropriate. The assessment of quality of care differed significantly between the two tools. Seventeen care trajectories classified as ‘Adequate’ or ‘Adequate plus’ by the APNCU were deemed ‘Inadequate’ by the CTP. This suggests that, despite a high number of visits, these women did not receive the minimal recommended content and timing of care. Conclusions: The CTP tool provides a more detailed assessment of the adequacy of antenatal care than the current standard index. However, guidelines for the content of antenatal care vary, and the tool does not at the moment grade over-use of interventions as ‘Inappropriate’. Further work needs to be done to refine the content items prior to larger scale testing of the impact of the new measure

Physical activity and medicine use: evidence from a population-based study

BACKGROUND: Few studies have investigated the association between physical activity practice and medicine use; data from these studies are inconsistent. The aim of this study was to evaluate the association between level of physical activity and medicine use in adults aged 20 years or more. METHODS: A population-based cross-sectional study was carried out in the first semester of 2002 in the urban area of Pelotas; a medium-sized Southern Brazilian city. Physical activity was assessed with the short version of the International Physical Activity Questionnaire. A physical activity score was created as the weekly time spent in moderate-intensity activities plus twice the weekly time spent in vigorous-intensity activities. Medicine use in the 15 days prior to the interview was also assessed. Adjusted analyses taking into account the sampling design was carried out using Poisson regression. Wald tests for heterogeneity and linear trend were used to calculate significance. RESULTS: Out of the 3,182 individuals interviewed, 41% were not sufficiently active according to current physical activity guidelines. Only 34% of the subjects did not use medicines in the previous 15 days, and 18% used three or more drugs in the same period. Level of physical activity was inversely associated with the number of medicines used both in the crude and in the adjusted analyses. CONCLUSION: There are well-documented benefits of physical activity for several chronic diseases in the literature. Data from the present study suggest that medicine use is also positively affected by physical activity behavior