Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2008/54953-0, 2008/04618-0, 2009/50113-0]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP

Spatial and temporal dynamics of the abundance of crustose calcareous algae on the southernmost coral reefs of the western Atlantic (Abrolhos Bank, Brazil)

Crustose calcareous algae (CCA) constitute one of the main reef builders on the Abrolhos Bank, Brazil. Once CCA taxonomy is locally understood, differences in growth-forms may be useful for the delimitation of taxa using characteristics such as the presence or absence of surface protuberances. Here, growth-forms were used to identify and quantify the most common CCA taxa on the shallow reefs (3-10 m) of the Abrolhos Bank to determine possible changes in the CCA community over a period of 10 years, and the ecological significance of CCA to local reefs was interpreted. The CCA assemblages were surveyed from 2006-2015 by using fixed photoquadrats at four sites in the inner (10-20 km from the mainland) and mid-shelf reefs (40-75 km from the mainland). The five most common CCA taxa were Pneophyllum conicum, the Lithophyllum kaiserii / Lithophyllum sp. complex, Melyvonnea erubescens, the Hydrolithon boergesenii / Porolithon onkodes complex and Peyssonelia sp. The overall mean CCA cover on the reefs was 20%. A comparison with a previous monitoring study in the same region indicated that the CCA cover nearly doubled from 2003-2008 to 2006-2015. This study reveals that the coral-killing species P. conicum dominated CCA flora on the shallow Abrolhos reefs in the last decade, and the local specific abundance of CCA slightly fluctuated over time and was species-and site-specific. The information obtained in this study contributes to the understanding of the ecology of the key calcifying components of the Abrolhos reefs and provides a useful baseline for exploring the responses of CCA to future environmental changes.PELDMudancas Climaticas scientific programmes of the Brazilian National Science Agency (CNPq)Brazilian IODP Program (CAPES/MEC)P&D Program ANP/BrasoilFAPERJDiretoria Pesquisa Cient, Inst Pesquisas, Jardim Bot Rio De Janeiro, Rua Pacheco Leao 915, BR-22460030 Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Biol, BR-21941599 Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Dept Oceanog, Ave Fernando Ferrari 514, BR-29090600 Vitoria, ES, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilUniv Fed Paraiba, Ctr Ciencias Aplicadas & Educ, Campus 4 Litoral Norte, BR-58297000 Rio Tinto, PB, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilANP/Brasoil: 48610.011015/2014-55Web of Scienc

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Physiological parameters for Prognosis in Abdominal Sepsis (PIPAS) Study : a WSES observational study

BackgroundTiming and adequacy of peritoneal source control are the most important pillars in the management of patients with acute peritonitis. Therefore, early prognostic evaluation of acute peritonitis is paramount to assess the severity and establish a prompt and appropriate treatment. The objectives of this study were to identify clinical and laboratory predictors for in-hospital mortality in patients with acute peritonitis and to develop a warning score system, based on easily recognizable and assessable variables, globally accepted.MethodsThis worldwide multicentre observational study included 153 surgical departments across 56 countries over a 4-month study period between February 1, 2018, and May 31, 2018.ResultsA total of 3137 patients were included, with 1815 (57.9%) men and 1322 (42.1%) women, with a median age of 47years (interquartile range [IQR] 28-66). The overall in-hospital mortality rate was 8.9%, with a median length of stay of 6days (IQR 4-10). Using multivariable logistic regression, independent variables associated with in-hospital mortality were identified: age > 80years, malignancy, severe cardiovascular disease, severe chronic kidney disease, respiratory rate >= 22 breaths/min, systolic blood pressure 4mmol/l. These variables were used to create the PIPAS Severity Score, a bedside early warning score for patients with acute peritonitis. The overall mortality was 2.9% for patients who had scores of 0-1, 22.7% for those who had scores of 2-3, 46.8% for those who had scores of 4-5, and 86.7% for those who have scores of 7-8.ConclusionsThe simple PIPAS Severity Score can be used on a global level and can help clinicians to identify patients at high risk for treatment failure and mortality.Peer reviewe

Global validation of the WSES Sepsis Severity Score for patients with complicated intra-abdominal infections : a prospective multicentre study (WISS Study)

Background: To validate a new practical Sepsis Severity Score for patients with complicated intra-abdominal infections (cIAIs) including the clinical conditions at the admission (severe sepsis/septic shock), the origin of the cIAIs, the delay in source control, the setting of acquisition and any risk factors such as age and immunosuppression. Methods: The WISS study (WSES cIAIs Score Study) is a multicenter observational study underwent in 132 medical institutions worldwide during a four-month study period (October 2014-February 2015). Four thousand five hundred thirty-three patients with a mean age of 51.2 years (range 18-99) were enrolled in the WISS study. Results: Univariate analysis has shown that all factors that were previously included in the WSES Sepsis Severity Score were highly statistically significant between those who died and those who survived (p <0.0001). The multivariate logistic regression model was highly significant (p <0.0001, R-2 = 0.54) and showed that all these factors were independent in predicting mortality of sepsis. Receiver Operator Curve has shown that the WSES Severity Sepsis Score had an excellent prediction for mortality. A score above 5.5 was the best predictor of mortality having a sensitivity of 89.2 %, a specificity of 83.5 % and a positive likelihood ratio of 5.4. Conclusions: WSES Sepsis Severity Score for patients with complicated Intra-abdominal infections can be used on global level. It has shown high sensitivity, specificity, and likelihood ratio that may help us in making clinical decisions.Peer reviewe

A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firing

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two shor

A novel role for MNTB neuron dendrites in regulating action potential amplitude and cell excitability during repetitive firing

Principal cells of the medial nucleus of the trapezoid body (MNTB) are simple round neurons that receive a large excitatory synapse (the calyx of Held) and many small inhibitory synapses on the soma. Strangely, these neurons also possess one or two short tufted dendrites, whose function is unknown. Here we assess the role of these MNTB cell dendrites using patch-clamp recordings, imaging and immunohistochemistry techniques. Using outside-out patches and immunohistochemistry, we demonstrate the presence of dendritic Na(+) channels. Current-clamp recordings show that tetrodotoxin applied onto dendrites impairs action potential (AP) firing. Using Na(+) imaging, we show that the dendrite may serve to maintain AP amplitudes during high-frequency firing, as Na(+) clearance in dendritic compartments is faster than axonal compartments. Prolonged high-frequency firing can diminish Na(+) gradients in the axon while the dendritic gradient remains closer to resting conditions; therefore, the dendrite can provide additional inward current during prolonged firing. Using electron microscopy, we demonstrate that there are small excitatory synaptic boutons on dendrites. Multi-compartment MNTB cell simulations show that, with an active dendrite, dendritic excitatory postsynaptic currents (EPSCs) elicit delayed APs compared with calyceal EPSCs. Together with high- and low-threshold voltage-gated K(+) currents, we suggest that the function of the MNTB dendrite is to improve high-fidelity firing, and our modelling results indicate that an active dendrite could contribute to a `dual` firing mode for MNTB cells (an instantaneous response to calyceal inputs and a delayed response to non-calyceal dendritic excitatory postsynaptic potentials)

Increased bursting glutamatergic neurotransmission in an auditory forebrain area of the zebra finch (Taenopygia guttata) induced by auditory stimulation

The caudomedial nidopallium (NCM) is a telencephalic area involved in auditory processing and memorization in songbirds, but the synaptic mechanisms associated with auditory processing in NCM are largely unknown. To identify potential changes in synaptic transmission induced by auditory stimulation in NCM, we used a slice preparation for path-clamp recordings of synaptic currents in the NCM of adult zebra finches (Taenopygia guttata) sacrificed after sound isolation followed by exposure to conspecific song or silence. Although post-synaptic GABAergic and glutamatergic currents in the NCM of control and song-exposed birds did not present any differences regarding their frequency, amplitude and duration after song exposure, we observed a higher probability of generation of bursting glutamatergic currents after blockade of GABAergic transmission in song-exposed birds as compared to controls. Both song-exposed males and females presented an increase in the probability of the expression of bursting glutamatergic currents, however bursting was more commonly seen in males where they appeared even without blocking GABAergic transmission. Our data show that song exposure changes the excitability of the glutamatergic neuronal network, increasing the probability of the generation of bursts of glutamatergic currents, but does not affect basic parameters of glutamatergic and GABAergic synaptic currents.Fundacao de Pesquisa do Estado de Sao PauloFundacao de Pesquisa do Estado de Sao Paulo [03/0419-0]National Institute of HealthFogarty International Collaborative Research AwardNational Institute of Health-Fogarty International Collaborative Research Award [TW006955]Coordenacao de Aperfeicoamento de Pessoal de Nivel SuperiorCoordenacao de Aperfeicoamento de Pessoal de Nivel Superio

Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons

Leao RM, Li S, Doiron B, Tzounopoulos T. Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons. J Neurophysiol 107: 3008-3019, 2012. First published February 29, 2012; doi:10.1152/jn.00660.2011.-Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba2+-sensitive, inwardly rectifying potassium conductance (K-ir). Variability in K-ir maximal conductance causes variations in the resting membrane potential (RMP). Low K-ir conductance depolarizes RMP to voltages above the threshold for activating subthreshold-persistent sodium channels (Na-p). Once Na-p channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information.National Institute on Deafness and Other Communication Disorders [R01 DC-007905]National Institute on Deafness and Other Communication DisordersNational Science Foundation [DMS-1121784]National Science Foundatio