Chemosensitivity of Phox2b-expressing retrotrapezoid neurons is mediated in part by input from 5-HT neurons.

KEY POINTS: Neurons of the retrotrapezoid nucleus (RTN) and medullary serotonin (5-HT) neurons are both candidates for central CO2 /pH chemoreceptors, but it is not known how interactions between them influence their responses to pH. We found that RTN neurons in brain slices were stimulated by exogenous 5-HT and by heteroexchange release of endogenous 5-HT, and these responses were blocked by antagonists of 5-HT7 receptors. The pH response of RTN neurons in brain slices was markedly reduced by the same antagonists of 5-HT7 receptors. Similar results were obtained in dissociated, primary cell cultures prepared from the ventral medulla, where it was also found that the pH response of RTN neurons was blocked by preventing 5-HT synthesis and enhanced by blocking 5-HT reuptake. Exogenous 5-HT did not enable latent intrinsic RTN chemosensitivity. RTN neurons may play more of a role as relays from other central and peripheral chemoreceptors than as CO2 sensors. ABSTRACT: Phox2b-expressing neurons in the retrotrapezoid nucleus (RTN) and serotonin (5-HT) neurons in the medullary raphe have both been proposed to be central respiratory chemoreceptors. How interactions between these two sets of neurons influence their responses to acidosis is not known. Here we recorded from mouse Phox2b+ RTN neurons in brain slices, and found that their response to moderate hypercapnic acidosis (pH 7.4 to ∼7.2) was markedly reduced by antagonists of 5-HT7 receptors. RTN neurons were stimulated in response to heteroexchange release of 5-HT, indicating that RTN neurons are sensitive to endogenous 5-HT. This electrophysiological behaviour was replicated in primary, dissociated cell cultures containing 5-HT and RTN neurons grown together. In addition, pharmacological inhibition of 5-HT synthesis in culture reduced RTN neuron chemosensitivity, and blocking 5-HT reuptake enhanced chemosensitivity. The effect of 5-HT on RTN neuron chemosensitivity was not explained by a mechanism whereby activation of 5-HT7 receptors enables or potentiates intrinsic chemosensitivity of RTN neurons, as exogenous 5-HT did not enhance the pH response. The ventilatory response to inhaled CO2 of mice was markedly decreased in vivo after systemic treatment with ketanserin, an antagonist of 5-HT2 and 5-HT7 receptors. These data indicate that 5-HT and RTN neurons may interact synergistically in a way that enhances the respiratory chemoreceptor response. The primary role of RTN neurons may be as relays and amplifiers of the pH response from 5-HT neurons and other chemoreceptors rather than as pH sensors themselves.

Coin Aspiration Presenting as Chronic Cough and Tracheoesophageal Fistula.

Chronic cough can be a diagnostic challenge in the pediatric population. Foreign body aspiration without typical signs and symptoms can often be overlooked as a cause of chronic cough in children. Coin aspirations in the trachea typically have a sagittal orientation on an anteroposterior (AP) chest radiograph. We report a rare case of a previously healthy five-year-old girl presenting with a chronic cough for five months caused by a coin with a coronal orientation on an AP chest radiograph. The coin, initially presumed to be lodged in the esophagus, was actually lodged in the cervical trachea, leading to the development of a tracheoesophageal fistula (TEF). Her AP chest radiograph showed a coronal, circular radio-opaque shadow and the lateral view a tangential radio-opaque shadow, prompting an initial evaluation by esophagogastroduodenoscopy, which was normal. She then underwent rigid bronchoscopy, revealing a coin lodged in the trachea along with a TEF. Surgical removal was achieved through an external approach with a vertical tracheotomy and insertion of a tracheostomy tube. Five days later, a repeat rigid bronchoscopy showed a well-healed TEF, and she was successfully decannulated. She was ultimately discharged home on room air and oral feeds. TEF as a complication of a foreign body lodged in the trachea or esophagus is rare but life-threatening. Foreign body aspiration should always be considered in the differential diagnosis when evaluating younger children with chronic cough.

Enhancing the Breast Histopathology Image Analysis for Cancer Detection Using Variational Autoencoder.

A breast tissue biopsy is performed to identify the nature of a tumour, as it can be either cancerous or benign. The first implementations involved the use of machine learning algorithms. Random Forest and Support Vector Machine (SVM) were used to classify the input histopathological images into whether they were cancerous or non-cancerous. The implementations continued to provide promising results, and then Artificial Neural Networks (ANNs) were applied for this purpose. We propose an approach for reconstructing the images using a Variational Autoencoder (VAE) and the Denoising Variational Autoencoder (DVAE) and then use a Convolutional Neural Network (CNN) model. Afterwards, we predicted whether the input image was cancerous or non-cancerous. Our implementation provides predictions with 73% accuracy, which is greater than the results produced by our custom-built CNN on our dataset. The proposed architecture will prove to be a new field of research and a new area to be explored in the field of computer vision using CNN and Generative Modelling since it incorporates reconstructions of the original input images and provides predictions on them thereafter.

Evaporation-driven self-assembly of binary and ternary colloidal polymer nanocomposites for abrasion resistant applications.

We harness the self-assembly of aqueous binary latex/silica particle blends during drying to fabricate films segregated by size in the vertical direction. We report for the first time the experimental drying of ternary colloidal dispersions and demonstrate how a ternary film containing additional small latex particles results in improved surface stability and abrasion resistance compared with a binary film. Through atomic force microscopy (AFM) and energy-dispersive X-ray spectroscopy (EDX), we show that the vertical distribution of filler particles and the surface morphologies of the films can be controlled by altering the evaporation rate and silica volume fraction. We report the formation of various silica superstructures at the film surface, which we attribute to a combination of diffusiophoresis and electrostatic interactions between particles. Brownian dynamics simulations of the final stages of solvent evaporation provide further evidence for this formation mechanism. We show how an additional small latex particle population results in an increased abrasion resistance of the film without altering its morphology or hardness. Our work provides a method to produce water-based coatings with enhanced abrasion resistance as well as valuable insights into the mechanisms behind the formation of colloidal superstructures.

Coronavirus Disease 2019 (COVID-19) Associated With Febrile Status Epilepticus in a Child.

Infection associated with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been named coronavirus disease 2019 (COVID-19). The emerging literature suggests that SARS-CoV-2 infection affects children of all age groups. COVID-19 as a cause of febrile seizures and status epilepticus is not yet reported in children. We report the case of a two-year-old child who presented to our pediatric intensive care unit with febrile status epilepticus and was diagnosed to have COVID-19 infection. The child recovered fully and was discharged home after three days.

Red Blood Cell Transfusion After Stage I Palliation Is Associated With Worse Clinical Outcomes.

Background Packed red blood cell transfusion may improve oxygen content in single-ventricle neonates, but its effect on clinical outcomes after Stage 1 palliation is unknown. Methods and Results Retrospective multicenter analysis of packed red blood cell transfusion exposures in neonates after Stage 1 palliation, excluding those with intraoperative mortality or need for extracorporeal membrane oxygenation. Transfusion practice variability was assessed, and multivariable regression used to identify transfusion risk factors. After propensity score adjustment for severity of illness, clinical outcomes were compared between transfused and nontransfused subjects. Of 396 subjects, 323 (82%) received 930 postoperative red blood cell transfusions. Packed red blood cell volume (median 9-42 mL/kg [P<0.0001]), donor exposures (1-2 [P<0.0001]), transfusion number (1-3 [P<0.0001]), and pretransfusion hemoglobin (12.1-13 g/dL, P=0.0049) varied between sites. Cyanosis (P=0.02), chest tube output (P=0.0003), and delayed sternal closure (P=0.0033) increased transfusion risk. Transfusion was associated with prolonged mechanical ventilation (6 [interquartile range 4, 12] versus 3 [1, 5] days, P=0.02) and intensive care unit stay (19 [12, 33] versus 9 [6, 19] days, P=0.016). When stratified by number of transfusions (0, 1, or >1), duration of mechanical ventilation (3 [1, 5] versus 4 [3, 6] versus 9 [5, 16] days [P<0.0001]) and intensive care unit stay (9 [6, 19] versus 13 [8, 25] versus 21 [13, 38] days [P<0.0001]) increased for those transfused more than once. Most subjects who died were transfused, though the association with mortality was not significant. Conclusions Packed red blood cell transfusion after Stage 1 palliation is common, and transfusion practice is variable. Transfusion is a significant predictor of longer intensive care unit stay and mechanical ventilation. Further studies to define evidence-based transfusion thresholds are warranted.

Efficacy of nonvenous medications for acute convulsive seizures: A network meta-analysis.

OBJECTIVE: This is a network meta-analysis of nonvenous drugs used in randomized controlled trials (RCTs) for treatment of acute convulsive seizures and convulsive status epilepticus. METHODS: Literature was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of acute convulsive seizures or status epilepticus with at least one of the study arms being a nonvenous medication. After demographic and outcome data extraction, a Bayesian network meta-analysis was performed and efficacy results were summarized using treatment effects and their credible intervals (CrI). We also calculated the probability of each route-drug combination being the most clinically effective for a given outcome, and provided their Bayesian hierarchical ranking. RESULTS: This meta-analysis of 16 studies found that intramuscular midazolam (IM-MDZ) is superior to other nonvenous medications regarding time to seizure termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI 2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI 0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most efficacious for seizure cessation within 10 minutes of administration (90.4% of participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour (78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence gaps resulting in small networks, routes/drugs included in some networks but not others, and some trials not being connected to any network. CONCLUSIONS: Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best efficacy data for the nonvenous treatment of acute convulsive seizures or status epilepticus.