Modulation of visual responses in the rat superior colliculus by metabotropic glutamate receptors

Neurones in the superficial layers of the superior colliculus (SSC) respond to novel visual events. Cells in the SSC project via neurones in the deep layer of the superior colliculus to motor nuclei which generate appropriate behavioural and avoidance responses to novel sensory stimuli. Glutamate is a neurotransmitter at the retino-collicular and cortico-collicular synapse. Glutamate receptors can be classified as either ionotropic or metabotropic (mGluRs). At present, 8 mGluRs have been cloned (mGluRl - mGluR8), and these can be divided into 3 groups based on sequence homology, pharmacology and coupling to 2nd messenger pathways. There is evidence that metabotropic glutamate receptors may be present on SSC neurones and SSC afferents. This study examines how mGluRs may modulate the response properties of visually responsive cells in the SSC. Iontophoretic application of pharmacological agents including selective mGluR agonists and antagonists are used to probe the functional effects of mGluR manipulation in an in- vivo preparation. All three groups of receptor appear to be activated by endogenous glutamate during visual synaptic transmission. Activation of Group I mGluRs (mGluR1 and mGluR5) cause a depression of the visual response. Activation of both Group II (mGluR2 and mGluR3) and Group III mGluRs (mGluR4, mGluR6, mGluR7 and mGluR8) causes a facilitation or inhibition of the visual response in individual neurones. Neurones in the SSC detect novel visual stimuli by producing a decline in the response to repeated stimuli, this is called habituation. Group III (but not Group I or Group II) mGluRs contribute to response habituation in the SSC and therefore have a functional role in detecting stimulus novelty. Activation of Group II receptors is dependent upon the intensity of the stimulus, probably due to their location away from the central region of the synapse. Immunohistochemical data presented here details the distribution of selected mGluRs in the sub-cortical retinofugal pathway of the rat, ferret and cat. Analysis shows that the distribution in these three species is dissimilar. This suggests that mGluRs may have different functional roles in visual processing in different species

Mitigation of ED Patient Boarding: Transferring Admissions from the Center City ED to Methodist

Objectives: Objectively analyze transferred patient transfers cases as far as LOS (length of stay), final diagnosis, and transfer failure. Assess patient satisfaction with the transfer process as means to identify areas for improvement as well as potential patient safety issues

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Correction: Ogrodnik et al. Exploring the Relationship between Cardiorespiratory Fitness and Executive Functioning in Adults with ADHD. <i>Brain Sci.</i> 2023, <i>13</i>, 673

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Exploring the Relationship between Cardiorespiratory Fitness and Executive Functioning in Adults with ADHD

Objective: Associations between measures of executive functioning (EF) and cardiorespiratory fitness (CRF) were examined for adults with and without ADHD. Method: Measures of executive functioning including the Stroop task, Wisconsin Card Sorting task, and Operation Span Task were completed virtually (n = 36 ADHD; n = 36 Control). Participants completed the Six-Minute Walk Test to estimate CRF. Results: Mean performance measures of executive function did not differ by group. However, higher estimated CRF was associated with better Stroop task performance, and the association was strongest for individuals with ADHD. Conclusion: In adults with ADHD, higher estimated CRF was associated with better inhibitory control, but not with other measures of executive functioning

Group II and III metabotropic glutamate receptors contribute to different aspects of visual response processing in the rat superior colliculus

Neurones in the superior colliculus (SC) respond to novel sensory stimuli and response habituation is a key feature of this. It is known that both ionotropic and metabotropic glutamate (mGlu) receptors participate in visual responses of superficial SC neurones. A feature of Group II and Group III mGlu receptors is that they may modulate specific neural pathways, possibly via presynaptic mechanisms. However, less is known about how this may relate to functions of systems in whole animals. We have therefore investigated whether these receptors affect specific attributes of visual responses in the superficial SC.Recordings were made from visually responsive neurones in anaesthetised rats, and agonists and antagonists of Group II and III mGlu receptors were applied iontophoretically at the recording site.We found that application of the Group III metabotropic glutamate receptor agonist l-2-amino-4-phosphonobutyric acid (l-AP4) produced an increase in visual response habituation, whilst Group III antagonists decreased habituation. These effects were independent of the response habituation mediated via GABAB receptors. In contrast, modulation of Group II mGlu receptors with the specific agonist LY354740 or the antagonist LY341495 did not affect response habituation, although these compounds did modulate visual responses. This suggests a specific role for Group III mGlu receptors in visual response habituation.The magnitude of Group II effects was smaller during presentation of low contrast stimuli compared with high contrast stimuli. This suggests that activation of Group II receptors may be activity dependent and that these receptors can translate this into a functional effect in adapting to high contrast stimuli

Immunocompromised patients with acute respiratory distress syndrome: Secondary analysis of the LUNG SAFE database

Background: The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p &lt; 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p &lt; 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation