Estimating the glutamate transporter surface density in distinct sub-cellular compartments of mouse hippocampal astrocytes.

Glutamate transporters preserve the spatial specificity of synaptic transmission by limiting glutamate diffusion away from the synaptic cleft, and prevent excitotoxicity by keeping the extracellular concentration of glutamate at low nanomolar levels. Glutamate transporters are abundantly expressed in astrocytes, and previous estimates have been obtained about their surface expression in astrocytes of the rat hippocampus and cerebellum. Analogous estimates for the mouse hippocampus are currently not available. In this work, we derive the surface density of astrocytic glutamate transporters in mice of different ages via quantitative dot blot. We find that the surface density of glial glutamate transporters is similar in 7-8 week old mice and rats. In mice, the levels of glutamate transporters increase until about 6 months of age and then begin to decline slowly. Our data, obtained from a combination of experimental and modeling approaches, point to the existence of stark differences in the density of expression of glutamate transporters across different sub-cellular compartments, indicating that the extent to which astrocytes limit extrasynaptic glutamate diffusion depends not only on their level of synaptic coverage, but also on the identity of the astrocyte compartment in contact with the synapse. Together, these findings provide information on how heterogeneity in the spatial distribution of glutamate transporters in the plasma membrane of hippocampal astrocytes my alter glutamate receptor activation out of the synaptic cleft.

Accuracy of after-hours trauma cervical spine CT reporting by radiology trainees: Experiences from two Australian teaching hospitals.

INTRODUCTION: Like many teaching hospitals in Australia, after-hours computed tomography (CT) reporting at our institution is undertaken by the on-call radiology registrar. The accuracy of these reports is important as management is often initiated based on the interim findings, prior to review by the consultant radiologist. A common exception to this approach is cervical CT (CCT), as many hospital protocols recommend patients to remain in spinal precautions until the report is finalised by a consultant, although there are very few studies to support this practice. METHODS: The interim registrar reports for all CCTs performed after-hours over a 12-month period were retrospectively reviewed. The final consultant report was used as the gold standard to establish accuracy of the registrar report. The primary outcome was discrepancy between the provisional and final reports. Any discrepancy was classified as either an 'overcall' or 'miss'. Discrepancies were graded by the RADPEER scoring system. RESULTS: A total of 1084 after-hours CCT studies were reviewed. The number of cases positive for injury was 37 (3.4%). The total number of discrepancies was 14 (discrepancy rate 1.3%), including 4 overcalls (0.3%) and 10 misses (0.9%). The discrepancy rates for junior and senior registrars were 1.7% and 0.7% respectively. Only 5 misses (0.5%) were considered clinically significant. CONCLUSION: Registrars reporting after-hours CCT have low rates of discrepancy with very few clinically significant misses. However, the reduced registrar sensitivity for detection of cervical injury highlights the ongoing importance of consultant review in the process of cervical spine clearance pathways.

Technical and practical tips for performing brain magnetic resonance imaging in premature neonates.

MR imaging of premature neonates is challenging due to their small size, need for temperature support and monitoring, and immature central nervous system. Use of MR compatible incubators and MR compatible monitoring apparatus, careful selection of imaging protocols, and real time review of images by a radiologist can streamline the imaging process and improve image quality. Imaging should be focused upon (1) the child's biorhythms (imaging during sleep cycles), (2) minimizing delays during transport and (3) delaying noisy MR sequences until the end of an examination. Successful imaging of premature neonates requires teamwork: advanced planning, careful communication among neonatologists, nurses, and radiologists, established imaging protocols, and coordination among team members during all aspects of the process.

Management strategies in a SEIR-type model of COVID 19 community spread.

The 2019 Novel Corona virus infection (COVID 19) is an ongoing public health emergency of international focus. Significant gaps persist in our knowledge of COVID 19 epidemiology, transmission dynamics, investigation tools and management, despite (or possibly because of) the fact that the outbreak is an unprecedented global threat. On the positive side, enough is currently known about the epidemic process to permit the construction of mathematical predictive models. In our work, we adapt a traditional SEIR epidemic model to the specific dynamic compartments and epidemic parameters of COVID 19, as it spreads in an age-heterogeneous community. We analyze management strategies of the epidemic course (as they were implemented through lockdown and reopening procedures in many of the US states and countries worldwide); however, to more clearly illustrate ideas, we focus on the example of a small scale college town community, with the timeline of control measures introduced in the state of New York. We generate predictions, and assess the efficiency of these control measures (closures, mobility restrictions, social distancing), in a sustainability context.

Exparel for Postoperative Pain Management: a Comprehensive Review.

PURPOSE OF REVIEW: Multimodal pain management is the most effective way to treat postsurgical pain. However, the use of opioids for acute pain management has unfortunately been a significant contributor to the current opioid epidemic. The use of opioids should be limited and only considered a "rescue" pain medication after other modalities of pain management have been utilized. RECENT FINDINGS: It may be difficult to curtail the use of opioids in the treatment of chronic pain; however, in the postsurgical setting, there is compelling evidence that an opioid-centric analgesic approach is not necessary for good patient outcomes and healthcare cost benefits. Opioid-related adverse effects are the leading cause of preventable harm in the hospital setting. After the realization in recent years of the many harmful effects of opioids, alternative regimens including the use of multimodal analgesia have become a standard practice in acute pain management. Exparel, a long-lasting liposomal bupivacaine local anesthetic agent, has many significant benefits in the management of postoperative pain. Overall, the literature suggests that Exparel may be a significant component for postoperative multimodal pain control owing to its efficacy and long duration of action.

Postoperative Management of Corneal Abrasions and Clinical Implications: a Comprehensive Review.

PURPOSE OF REVIEW: Total patient care is of extreme importance during the administration of anesthesia. Proper care of the eye is necessary during all anesthetic administrations, especially during the administration of general anesthesia or monitored anesthesia care. By paying attention to details, the likelihood of an occurrence of eye injuries is reduced. RECENT FINDINGS: Though perioperative eye injuries are rare during general anesthesia, they do account for 2-3% of claims against anesthesiologists. Ocular injuries may occur during general anesthesia even when tape has been utilized for eye closure. Corneal abrasions are the most common injuries that have been attributed to direct trauma to the eye, exposure keratopathy, or chemical injury. Using a hydrogel patch during general anesthesia is also associated with more frequent corneal injury than previously thought. Prevention of anesthesia-related eye injuries assumes a high priority since the eye is one of the major sense organs of the body. The eye can be damaged during anesthesia for both non-ophthalmic and ophthalmic surgeries.

Complications in Pediatric Regional Anesthesia: An Analysis of More than 100,000 Blocks from the Pediatric Regional Anesthesia Network.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Complications in pediatric regional anesthesia are rare, so a large sample size is necessary to quantify risk. The Pediatric Regional Anesthesia Network contains data on more than 100,000 blocks administered at more than 20 children's hospitals. This study analyzed the risk of major complications associated with regional anesthesia in children. METHODS: This is a prospective, observational study of routine clinical practice. Data were collected on every regional block placed by an anesthesiologist at participating institutions and were uploaded to a secure database. The data were audited at multiple points for accuracy. RESULTS: There were no permanent neurologic deficits reported (95% CI, 0 to 0.4:10,000). The risk of transient neurologic deficit was 2.4:10,000 (95% CI, 1.6 to 3.6:10,000) and was not different between peripheral and neuraxial blocks. The risk of severe local anesthetic systemic toxicity was 0.76:10,000 (95% CI, 0.3 to 1.6:10,000); the majority of cases occurred in infants. There was one epidural abscess reported (0.76:10,000, 95% CI, 0 to 4.8:10,000). The incidence of cutaneous infections was 0.5% (53:10,000, 95% CI, 43 to 64:10,000). There were no hematomas associated with neuraxial catheters (95% CI, 0 to 3.5:10,000), but one epidural hematoma occurred with a paravertebral catheter. No additional risk was observed with placing blocks under general anesthesia. The most common adverse events were benign catheter-related failures (4%). CONCLUSIONS: The data from this study demonstrate a level of safety in pediatric regional anesthesia that is comparable to adult practice and confirms the safety of placing blocks under general anesthesia in children.

Distinct behavior of myelomonocytic cells and CD8 T cells underlies the hepatic response to Listeria monocytogenes.

Background: The immune response to Listeria monocytogenes (LM) is characterized by formation of leukocyte rich foci of infection in liver and spleen.  Although much has been gained in our understanding of immune response through the study of LM, little is known about spatio-temporal regulation of immune response to Listeria in liver. Methods: We utilize a combination of molecular, genetic and intravital microscopic approaches to gain insight into the dynamics of foci and leukocyte behavior during hepatic Listeriosis.  Results: LM foci efficiently exclude blood flow, indicating the presence of a barrier separating the foci and healthy tissue.  Despite this barrier, sinusoidal myelomonocytic cells readily enter or transiently interact with cells at the edge of foci of infection.  Next, utilizing L9.6 transgenic CD8 + T cells specific for an endogenously processed LM antigen, p60 217-225, along with LM deficient in this epitope, we define the role of TCR in T cell migratory behavior in infected liver.  Surprisingly, T cell behavior varies with micro-anatomic locale.  Near foci, non-specific adhesion mechanisms dominate lymphocyte behavior.  Antigen specific effects on motility became detectable only distal to foci.  Conclusions: These data suggest that LM antigens act in a paracrine manner to mediate protection from Listeriosis in the liver.

Pediatric neuro MRI: tricks to minimize sedation.

Magnetic resonance imaging (MRI) is the workhorse modality in pediatric neuroimaging because it provides excellent soft-tissue contrast without ionizing radiation. Until recently, studies were uninterpretable without sedation; however, given development of shorter sequences, sequences that correct for motion, and studies showing the potentially deleterious effects of sedation on immature laboratory animals, it is prudent to minimize sedation when possible. This manuscript provides basic guidelines for performing pediatric neuro MRI without sedation by both modifying technical factors to reduce scan time and noise, and using a multi-disciplinary team to coordinate imaging with the patient's biorhythms.

Inflammasome-mediated inhibition of Listeria monocytogenes-stimulated immunity is independent of myelomonocytic function.

Activation of the Nlrc4 inflammasome results in the secretion of IL-1ß and IL-18 through caspase-1 and induction of pyroptosis. L. monocytogenes engineered to activate Nlrc4 by expression of Legionella pneumophilia flagellin (L. monocytogenes L.p.FlaA) are less immunogenic for CD8(+) T cell responses than wt L. monocytogenes. It is also known that IL-1ß orchestrates recruitment of myelomonocytic cells (MMC), which have been shown to interfere with T cell-dendritic cells (DC) interactions in splenic white pulp (WP), limiting T cell priming and protective immunity. We have further analyzed the role of MMCs in the immunogenicity of L. monocytogenes L.p.FlaA. We confirmed that MMCs infiltrate the WP between 24-48 hours in response to wt L. monocytogenes infection and that depletion of MMCs enhances CD8(+) T cell priming and protective memory. L. monocytogenes L.p.FlaA elicited accelerated recruitment of MMCs into the WP. While MMCs contribute to control of L. monocytogenes L.p.FlaA, MMC depletion did not increase immunogenicity of L.p.FlaA expressing strains. There was a significant decrease in L. monocytogenes L.p.FlaA in CD8α(+) DCs independent of MMCs. These findings suggest that limiting inflammasome activation is important for bacterial accumulation in CD8α(+) DCs, which are known to be critical for T cell response to L. monocytogenes.