The Paradox of Astroglial Ca2+ Signals at the Interface of Excitation and Inhibition

Astroglial networks constitute a non-neuronal communication system in the brain and are acknowledged modulators of synaptic plasticity. A sophisticated set of transmitter receptors in combination with distinct secretion mechanisms enables astrocytes to sense and modulate synaptic transmission. This integrative function evolved around intracellular Ca2+ signals, by and large considered as the main indicator of astrocyte activity. Regular brain physiology meticulously relies on the constant reciprocity of excitation and inhibition (E/I). Astrocytes are metabolically, physically, and functionally associated to the E/I convergence. Metabolically, astrocytes provide glutamine, the precursor of both major neurotransmitters governing E/I in the central nervous system (CNS): glutamate and γ-aminobutyric acid (GABA). Perisynaptic astroglial processes are structurally and functionally associated with the respective circuits throughout the CNS. Astonishingly, in astrocytes, glutamatergic as well as GABAergic inputs elicit similar rises in intracellular Ca2+ that in turn can trigger the release of glutamate and GABA as well. Paradoxically, as gliotransmitters, these two molecules can thus strengthen, weaken or even reverse the input signal. Therefore, the net impact on neuronal network function is often convoluted and cannot be simply predicted by the nature of the stimulus itself. In this review, we highlight the ambiguity of astrocytes on discriminating and affecting synaptic activity in physiological and pathological state. Indeed, aberrant astroglial Ca2+ signaling is a key aspect of pathological conditions exhibiting compromised network excitability, such as epilepsy. Here, we gather recent evidence on the complexity of astroglial Ca2+ signals in health and disease, challenging the traditional, neuro-centric concept of segregating E/I, in favor of a non-binary, mutually dependent perspective on glutamatergic and GABAergic transmission

A systematic review opens the black box of “usual care” in stroke rehabilitation control groups and finds a black hole

INTRODUCTION: In experimental trials, new methods are tested against the “best” or “usual” care. To appraise control group (CG) interventions provided as “usual care,” we focused on stroke as a leading cause of disability demanding rehabilitation as a complex intervention. EVIDENCE ACQUISITION: For this methodological appraisal, we conducted a systematic review of RCTs without timespan limitation. The PICO included stroke survivors, rehabilitation, control group intervention, lower limb function. To assess the risk of bias, we used the Cochrane risk of bias tool (RoB). we identified the terminology describing the CG Program (CGP), performed a knowledge synthesis and conducted a frequency analysis of provided interventions. EVIDENCE SYNTHESIS: we included 155 publications. 13.6% of the articles did not describe the CG, and 11.6% indicated only the professionals involved. In the remaining 116 studies, three studies provided an intervention according to specific guidelines, 106 different “usual care” CGPs were detected, with nine proposed twice and two between four and five times. The most adopted terminology to state “usual care” was “conventional physiotherapy.” CONCLUSIONS: This study shows that usual care in CG does not actually exist, as both specific terminology and consistency within CGP contents are missing. Reporting guidelines should give better assistance on this issue. These results should be verified in other fields

Spontaneous membrane-less multi-compartmentalisation via aqueous two-phase separation in complex coacervate microdroplets

Polyelectrolyte/nucleotide multiphase complex coacervate droplets are produced by internalized aqueous two-phase separation and used for the spatially dependent chemical transfer of sugar molecules, providing a step towards the development of membrane-free "organelles" within coacervate-based protocells

Association between exposure to particulate matter and hospital admissions for respiratory disease in children

Con el objetivo de estimar la asociación entre exposición al PM2.5 e internaciones por enfermedades respiratorias en niños, fue realizado estudio ecológico de series temporales con indicadores diarios de internación por enfermedades respiratorias, en niños de cero a diez años de edad, residentes en Piracicaba, SP (período entre 1° de agosto de 2011 y 31 de julio de 2012. Se utilizó modelo aditivo generalizado de la regresión de Poisson. Los riesgos relativos fueron RR= 1,008; IC95% 1,001; 1,016 para el lag 1 y RR= 1,009; IC95% 1,001; 1,017 para el lag 3. El incremento de 10 μg/m3 de PM2.5 implicó aumento en el riesgo relativo entre 7,9 y 8,6 puntos porcentuales. Se concluyó que la exposición al material particulado con menos de 2,5 micras de diámetro aerodinámico estuvo asociada con las internaciones por enfermedades respiratorias en niños.The aim of this study was to estimate the association between exposure to particulate matter less than 2.5 microns in diameter and hospitalization for respiratory disease. It was an ecological time series study with daily indicators of hospitalization for respiratory diseases in children up to 10 years old, living in Piracicaba, SP, Southeastern Brazil, between August 1, 2011 and July 31, 2012. A generalized additive Poisson regression model was used. The relative risks were RR = 1.008; 95%CI 1.001;1.016 for lag 1 and RR = 1.009; 95%CI 1.001;1.017 for lag 3. The increment of 10 μg/m3in particulate matter less than 2.5 microns in diameter implies increase in relative risk of between 7.9 and 8.6 percentage points. In conclusion, exposure to particulate matter less than 2.5 microns in diameter was associated with hospitalization for respiratory disease in children.O objetivo desse estudo foi estimar a associação entre exposição a material particulado com menos de 2,5 micra de diâmetro aerodinâmico e internações por doenças respiratórias em crianças. Foi realizado estudo ecológico de séries temporais com indicadores diários de internação por doenças respiratórias, em crianças de zero a dez anos de idade, residentes em Piracicaba, SP, entre 1º de agosto de 2011 e 31 de julho de 2012. Utilizou-se modelo aditivo generalizado da regressão de Poisson. Os riscos relativos foram RR = 1,008; IC95% 1,001;1,016 para o lag 1 e RR = 1,009; IC95% 1,001;1,017 para o lag 3. O incremento de 10 μg/m 3 de material particulado com menos de 2,5 micra de diâmetro implicou aumento no risco relativo entre 7,9 e 8,6 pontos percentuais. Concluiu-se que a exposição ao material particulado com menos de 2,5 micra de diâmetro aerodinâmico esteve associada às internações por doenças respiratórias em crianças

Serum Magnesium Concentrations and All-cause, Cardiovascular, and Cancer Mortality among U.S. Adults: Results from The NHANES I Epidemiologic Follow-up Study

Background Few studies have examined the associations of serum magnesium (Mg) concentrations with total and cause-specific mortality in a nationally representative sample of US adults. We investigate the dose–response relationships of baseline serum Mg concentrations with risk of mortalities in a large, nationally representative sample of US adults. Methods We analyzed prospective data of 14,353 participants aged 25–74 years with measures of serum Mg concentrations at baseline (1971–1975) from the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS). Mortality data was linked through December 31, 2011. We estimated the mortality hazard ratios (HRs), for participants within serum Mg categories of <0.7, 0.7–0.74, 0.75–0.79, 0.8–0.89 (referent), 0.9–0.94, 0.95–0.99, and ≥1.0 mmol/L using weighted multivariate-adjusted Cox proportional hazards models. Results During a median follow-up of 28.6 years, 9012 deaths occurred, including 3959 CVD deaths, 1923 cancer deaths, and 708 stroke deaths. The multivariate-adjusted HRs (95% CIs) of all-cause mortality across increasing categories of Mg were 1.34 (1.02, 1.77), 0.94 (0.75, 1.18), 1.08 (0.97, 1.19), 1.00 (referent), 1.05 (0.95, 1.16), 0.96 (0.79, 1.15), and 0.98 (0.76, 1.26). Similar trends were observed for cancer (HRs for serum Mg < 0.7: 1.39, 95% CI: 0.83, 2.32) and CVD mortality (HRs for serum Mg < 0.7: 1.28, 95% CI: 0.81, 2.02) but were not statistically significant. An elevated risk for stroke mortality was observed among participants with serum Mg < 0.70 mmol/L (HR: 2.55, 95% CI: 1.18, 5.48). Conclusions Very low serum Mg concentrations were significantly associated with an increased risk of all-cause mortality in US adults