From Admission to Discharge-A Total Friction Burn Review from a Single Institution.

While most friction burns are adequately managed in an outpatient setting, many may require hospital admission, operative excision, and extended care. To this day, there is a wide variance in friction burn management. Our goal is to review the etiology, management, and outcomes of such burns warranting hospitalization. We conducted a retrospective review of all friction burns admitted to a single, American Burn Association-verified burn center from January 1, 2016 to December 31, 2020. A total of 28 (34%) patients required surgery for their friction burns and 15 (18%) ultimately required a split-thickness skin graft. The mean number of operations was 2.4 (95% CI 1.6-3.1). Overall, the operative group was younger (29.9 vs 38.3 years, P = .026), more likely to have a concomitant traumatic brain injury (25% vs 7%, P = .027), and had a longer hospital length of stay (17.5 vs 3.9 days, P < .001). Both groups had a similar overall TBSA (8.5% vs 10.0%, P = .35), but the operative group had a larger surface area comprised of third-degree burns (3.05% vs 0.2%, P < .001). Overall, friction burns resulting in hospital admission are associated with high-energy traumatic mechanisms and concomitant injuries. Patients who need operative intervention for their burns typically require multiple procedures often culminating in a split-thickness skin graft. While non-operative management of friction burns with topical agents has been found to be successful, patients with higher injury severity scores should be monitored very closely as they may require surgical excision.

Temperature Profiles of Sunlight-Exposed Surfaces in a Desert Climate: Determining the Risk for Pavement Burns.

Plentiful sunlight and high temperatures in desert climates cause burn injuries from contact with sun-exposed surfaces. The peak temperature, times, and surfaces of greatest risk are not well described. This work recorded temperature measurements of six materials in a desert climate. Surface temperatures of asphalt, brick, concrete, sand, porous rock, and galvanized metal were measured throughout the summer, along with ambient temperature, and sunlight intensity. Samples were placed in both shade and direct sunlight for evaluation of sunlight effect. Seventy-five thousand individual measurements were obtained from March to August 2020. Maximum recorded temperatures for sunlight-exposed porous rock were 170°F, asphalt 166°F, brick 152°F, concrete 144°F, metal 144°F, and sand 143°F, measured on August 6, 2020 at 2:10 pm, when ambient temperature was 120°F and solar irradiation 940 W/m2. Sunlight-exposed materials ranged 36 to 56°F higher than shaded materials measured at the same time. The highest daily temperatures were achieved between 2:00 and 4:00 pm due to maximum solar irradiance. Contour plots of surface temperature as a function of both solar irradiation and time of day were created for all materials tested. A computational fluid dynamics model was created to validate the data and serve as a predictive model based upon temperature and sunlight inputs. This information is useful to inform the public of the risks of contact burn due to sunlight-exposed surfaces in a desert climate.

Electronic Cigarette-Related Injuries Presenting to Five Large Burn Centers, 2015-2019.

Electronic cigarettes are advertised as safer alternatives to traditional cigarettes yet cause serious injury. U.S. burn centers have witnessed a rise in both inpatient and outpatient visits to treat thermal injuries related to their use. A multicenter retrospective chart review of American Burn Association burn registry data from five large burn centers was performed from January 2015 to July 2019 to identify patients with electronic cigarette-related injuries. A total of 127 patients were identified. Most sustained less than 10% total body surface area burns (mean 3.8%). Sixty-six percent sustained second-degree burns. Most patients (78%) were injured while using their device. Eighteen percent of patients reported spontaneous device combustion. Two patients were injured while changing their device battery, and two were injured modifying their device. Three percent were injured by secondhand mechanism. Burn injury was the most common injury pattern (100%), followed by blast injury (3.93%). Flame burns were the most common (70%) type of thermal injury; however, most patients sustained a combination-type injury secondary to multiple burn mechanisms. The most injured body region was the extremities. Silver sulfadiazine was the most common agent used in the initial management of thermal injuries. Sixty-three percent of patients did not require surgery. Of the 36% requiring surgery, 43.4% required skin grafting. Multiple surgeries were uncommon. Our data recognize electronic cigarette use as a public health problem with the potential to cause thermal injury and secondary trauma. Most patients are treated on an inpatient basis although most patients treated on an outpatient basis have good outcomes.

Are Self-Inflicted Stab Wounds Less Severe Than Assaults? Analysis of Injury and Severity by Intent.

BACKGROUND: Although there is evidence that self-inflicted abdominal stab wounds are less severe than those from assault, it is unclear if this is true in other anatomic regions. This study compares severity and injury pattern between self-inflicted stab wounds (SISWs) and wounds from assault (ASW). MATERIALS AND METHODS: Stab wounds from our level I trauma registry from 2013 to 2018 were reviewed. Data included age, gender, self-inflicted versus assault, psychiatric or substance use history, anatomic location, operative intervention, injury severity, length of stay, and outcomes. RESULTS: Over the study period, 1390 patients were identified. History of psychiatric diagnoses or previous suicide attempts was more frequent in SISWs (47% versus 6.5%, P < 0.01; 35% versus 0.4%, P < 0.01). SISWs had a higher incidence of wounds to the neck and abdomen (44% versus 11%, P < 0.01; and 34% versus 26%, P = 0.02). Overall, injuries from ASW had a higher injury severity score, but more procedures were performed on SISWs (46% versus 34%, P < 0.01). SISWs to the neck were more likely to undergo procedures (26% versus 15%, P = 0.04). Median hospital charges were higher in patients with SISWs ($58.6 K versus $39.4 K, P < 0.01). CONCLUSIONS: SISWs have a distinct pattern of injuries, more commonly to the neck and abdomen, when compared with injuries resulting from ASW. The patients with SISWs have a higher rate of procedures, longer length of stay, and higher hospital charges despite low injury severity overall.

Homeostatic Plasticity in the Hippocampus Facilitates Memory Extinction.

Correlated activity in the hippocampus drives synaptic plasticity that is necessary for the recruitment of neuronal ensembles underlying fear memory. Sustained neural activity, on the other hand, may trigger homeostatic adaptations. However, whether homeostatic plasticity affects memory function remains unknown. Here, we use optogenetics to induce cell autonomous homeostatic plasticity in CA1 pyramidal neurons and granule cells of the hippocampus. High-frequency spike trains applied for 10 min decreased the number of excitatory spine synapses and increased the number of inhibitory shaft synapses. This activity stopped dendritic spine formation via L-type voltage-dependent calcium channel activity and protein synthesis. Applied selectively to the ensemble of granule cells encoding a contextual fear memory, the spike trains impaired memory recall and facilitated extinction. Our results indicate that homeostatic plasticity triggered by optogenetic neuronal firing alters the balance between excitation and inhibition in favor of memory extinction.

Activity-dependent inhibitory synapse remodeling through gephyrin phosphorylation.

Maintaining a proper balance between excitation and inhibition is essential for the functioning of neuronal networks. However, little is known about the mechanisms through which excitatory activity can affect inhibitory synapse plasticity. Here we used tagged gephyrin, one of the main scaffolding proteins of the postsynaptic density at GABAergic synapses, to monitor the activity-dependent adaptation of perisomatic inhibitory synapses over prolonged periods of time in hippocampal slice cultures. We find that learning-related activity patterns known to induce N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation and transient optogenetic activation of single neurons induce within hours a robust increase in the formation and size of gephyrin-tagged clusters at inhibitory synapses identified by correlated confocal electron microscopy. This inhibitory morphological plasticity was associated with an increase in spontaneous inhibitory activity but did not require activation of GABAA receptors. Importantly, this activity-dependent inhibitory plasticity was prevented by pharmacological blockade of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), it was associated with an increased phosphorylation of gephyrin on a site targeted by CaMKII, and could be prevented or mimicked by gephyrin phospho-mutants for this site. These results reveal a homeostatic mechanism through which activity regulates the dynamics and function of perisomatic inhibitory synapses, and they identify a CaMKII-dependent phosphorylation site on gephyrin as critically important for this process.

Shaping inhibition: activity dependent structural plasticity of GABAergic synapses.

Inhibitory transmission through the neurotransmitter γ-aminobutyric acid (GABA) shapes network activity in the mammalian cerebral cortex by filtering synaptic incoming information and dictating the activity of principal cells. The incredibly diverse population of cortical neurons that use GABA as neurotransmitter shows an equally diverse range of mechanisms that regulate changes in the strength of GABAergic synaptic transmission and allow them to dynamically follow and command the activity of neuronal ensembles. Similarly to glutamatergic synaptic transmission, activity-dependent functional changes in inhibitory neurotransmission are accompanied by alterations in GABAergic synapse structure that range from morphological reorganization of postsynaptic density to de novo formation and elimination of inhibitory contacts. Here we review several aspects of structural plasticity of inhibitory synapses, including its induction by different forms of neuronal activity, behavioral and sensory experience and the molecular mechanisms and signaling pathways involved. We discuss the functional consequences of GABAergic synapse structural plasticity for information processing and memory formation in view of the heterogenous nature of the structural plasticity phenomena affecting inhibitory synapses impinging on somatic and dendritic compartments of cortical and hippocampal neurons.

Activity-dependent structural plasticity of perisynaptic astrocytic domains promotes excitatory synapse stability.

BACKGROUND: Excitatory synapses in the CNS are highly dynamic structures that can show activity-dependent remodeling and stabilization in response to learning and memory. Synapses are enveloped with intricate processes of astrocytes known as perisynaptic astrocytic processes (PAPs). PAPs are motile structures displaying rapid actin-dependent movements and are characterized by Ca(2+) elevations in response to neuronal activity. Despite a debated implication in synaptic plasticity, the role of both Ca(2+) events in astrocytes and PAP morphological dynamics remain unclear. RESULTS: In the hippocampus, we found that PAPs show extensive structural plasticity that is regulated by synaptic activity through astrocytic metabotropic glutamate receptors and intracellular calcium signaling. Synaptic activation that induces long-term potentiation caused a transient PAP motility increase leading to an enhanced astrocytic coverage of the synapse. Selective activation of calcium signals in individual PAPs using exogenous metabotropic receptor expression and two-photon uncaging reproduced these effects and enhanced spine stability. In vivo imaging in the somatosensory cortex of adult mice revealed that increased neuronal activity through whisker stimulation similarly elevates PAP movement. This in vivo PAP motility correlated with spine coverage and was predictive of spine stability. CONCLUSIONS: This study identifies a novel bidirectional interaction between synapses and astrocytes, in which synaptic activity and synaptic potentiation regulate PAP structural plasticity, which in turn determines the fate of the synapse. This mechanism may represent an important contribution of astrocytes to learning and memory processes.

Molecular and functional asymmetry at a vertebrate electrical synapse.

Electrical synapses are abundant in the vertebrate brain, but their functional and molecular complexities are still poorly understood. We report here that electrical synapses between auditory afferents and goldfish Mauthner cells are constructed by apposition of hemichannels formed by two homologs of mammalian connexin 36 (Cx36) and that, while Cx35 is restricted to presynaptic hemiplaques, Cx34.7 is restricted to postsynaptic hemiplaques, forming heterotypic junctions. This molecular asymmetry is associated with rectification of electrical transmission that may act to promote cooperativity between auditory afferents. Our data suggest that, in similarity to pre- and postsynaptic sites at chemical synapses, one side in electrical synapses should not necessarily be considered the mirror image of the other. While asymmetry based on the presence of two Cx36 homologs is restricted to teleost fish, it might also be based on differences in posttranslational modifications of individual connexins or in the complement of gap junction-associated proteins.

Gap junction-mediated electrical transmission: regulatory mechanisms and plasticity.

The term synapse applies to cellular specializations that articulate the processing of information within neural circuits by providing a mechanism for the transfer of information between two different neurons. There are two main modalities of synaptic transmission: chemical and electrical. While most efforts have been dedicated to the understanding of the properties and modifiability of chemical transmission, less is still known regarding the plastic properties of electrical synapses, whose structural correlate is the gap junction. A wealth of data indicates that, rather than passive intercellular channels, electrical synapses are more dynamic and modifiable than was generally perceived. This article will discuss the factors determining the strength of electrical transmission and review current evidence demonstrating its dynamic properties. Like their chemical counterparts, electrical synapses can also be plastic and modifiable. This article is part of a Special Issue entitled: The Communicating junctions, roles and dysfunctions.

Trafficking of gap junction channels at a vertebrate electrical synapse in vivo.

Trafficking and turnover of transmitter receptors required to maintain and modify the strength of chemical synapses have been characterized extensively. In contrast, little is known regarding trafficking of gap junction components at electrical synapses. By combining ultrastructural and in vivo physiological analysis at identified mixed (electrical and chemical) synapses on the goldfish Mauthner cell, we show here that gap junction hemichannels are added at the edges of GJ plaques where they dock with hemichannels in the apposed membrane to form cell-cell channels and, simultaneously, that intact junctional regions are removed from centers of these plaques into either presynaptic axon or postsynaptic dendrite. Moreover, electrical coupling is readily modified by intradendritic application of peptides that interfere with endocytosis or exocytosis, suggesting that the strength of electrical synapses at these terminals is sustained, at least in part, by fast (in minutes) turnover of gap junction channels. A peptide corresponding to a region of the carboxy terminus that is conserved in Cx36 and its two teleost homologs appears to interfere with formation of new gap junction channels, presumably by reducing insertion of hemichannels on the dendritic side. Thus, our data indicate that electrical synapses are dynamic structures and that their channels are turned over actively, suggesting that regulated trafficking of connexons may contribute to the modification of gap junctional conductance.

Variability of distribution of Ca(2+)/calmodulin-dependent kinase II at mixed synapses on the mauthner cell: colocalization and association with connexin 35.

In contrast to chemical transmission, few proteins have been shown associated with gap junction-mediated electrical synapses. Mixed (electrical and glutamatergic) synaptic terminals on the teleost Mauthner cell known as "Club endings" constitute because of their unusual large size and presence of connexin 35 (Cx35), an ortholog of the widespread mammalian Cx36, a valuable model for the study of electrical transmission. Remarkably, both components of their mixed synaptic response undergo activity-dependent potentiation. Changes in electrical transmission result from interactions with colocalized glutamatergic synapses, the activity of which leads to the activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII), required for the induction of changes in both forms of transmission. However, the distribution of this kinase and potential localization to electrical synapses remains undetermined. Taking advantage of the unparalleled experimental accessibility of Club endings, we explored the presence and intraterminal distribution of CaMKII within these terminals. Here we show that (1) unlike other proteins, both CaMKII labeling and distribution were highly variable between contiguous contacts, and (2) CaMKII was not restricted to the periphery of the terminals, in which glutamatergic synapses are located, but also was present at the center in which gap junctions predominate. Accordingly, double immunolabeling indicated that Cx35 and CaMKII were colocalized, and biochemical analysis showed that these proteins associate. Because CaMKII characteristically undergoes activity-dependent translocation, the observed variability of labeling likely reflects physiological differences between electrical synapses of contiguous Club endings, which remarkably coexist with differing degrees of conductance. Together, our results indicate that CaMKII should be considered a component of electrical synapses, although its association is nonobligatory and likely driven by activity.

An immunochemical marker for goldfish Mauthner cells.

The Mauthner (M-) cells are pair of large reticulospinal neurons that mediate tail-flip escape responses in fish. Exploring the co-localization of scaffold and gap junction proteins at mixed (electrical and chemical) synapses, we found that the use of a particular antibody against the scaffold protein Zonula Occludens-2 (ZO-2) resulted in labeling of these cells. We show here that this staining is restricted to the Mauthner cell and evenly distributed along its dendrites and axon, also prominent in small dendritic and axonal processes. Because the observed labeling is non-specific, we suggest that the antibody might recognize a soluble protein that is primarily expressed in the Mauthner cells. While the identity of this protein is presently unknown, the use of this antibody should facilitate the identification of the Mauthner cell and its fine processes during anatomical and immunohistochemical studies, which otherwise require intracellular injection of tracer molecules during electrophysiological recordings.

Interaction between connexin35 and zonula occludens-1 and its potential role in the regulation of electrical synapses.

Although regulation of chemical transmission is known to involve the interaction of receptors with scaffold proteins, little is known about the existence of protein-protein interactions in regulating gap junction-mediated electrical synapses. The scaffold protein zonula-occludens-1 (ZO-1), a member of the MAGUK family of proteins, was reported to interact with several connexins (Cxs). We show here that ZO-1 extensively colocalizes with Cx35 at identifiable "mixed" (electrical and chemical) contacts on goldfish Mauthner cells, a model synapse for the study of vertebrate electrical transmission where it is possible to correlate physiological properties with molecular composition. Further, our analysis indicates that these proteins directly interact at goldfish electrical synapses. In contrast to Cx43, which interacts with ZO-1 via the PDZ2 domain, Cx35 interacts with ZO-1 via the PDZ1 domain, and this association is of lower affinity. The properties of the ZO-1/Cx35 association suggest the existence of a more dynamic relation between these two proteins, possibly including a role of ZO-1 in regulating gap junctional conductance at these highly modifiable electrical synapses. The interaction of ZO-1 with conserved regions of the C termini of Cx35/Cx36 orthologs may have a common function at electrical synapses of mammals and other vertebrates.