Perampanel in routine clinical use across Europe: Pooled, multicenter, observational data.

OBJECTIVE: To pool observational data on the routine use of perampanel to obtain information on real-world outcomes and data in populations typically underrepresented in clinical trials. METHODS: Individual-level data of people with epilepsy treated with perampanel at 45 European centers were merged into a single dataset. Prespecified outcomes were: 1-year retention rate, 1-year seizure freedom rate (duration ≥6 months), and incidence of treatment-emergent adverse events (TEAEs). In addition, relationships were explored with logistic regression analyses. RESULTS: The full analysis set comprised 2396 people: 95% had focal seizures; median epilepsy duration was 27 years; median number of concomitant antiepileptic drugs (AEDs) was 2; and median prior AEDs was 6. One-year retention rate was 48% (1117/2332; 95% confidence interval [CI] 46-50%), and 1-year seizure-free rate (≥6-month duration) was 9.2% (74/803; 95% CI 7-11%). Median treatment duration was 11.3 months (1832 patient-years); median dose was 8 mg. In 388 individuals with available data at 3, 6, and 12 months, responder rates were 42%, 46%, and 39%, respectively. During the first year, TEAEs were reported in 68% of participants (1317/1497; 95% CI 66-70%). Logistic regression found higher age at perampanel initiation was associated with higher seizure-free rate, and higher number of prior AEDs with lower seizure-free rate and lower rates of somatic TEAEs. In 135 individuals aged ≥65 years, 1-year retention rate was 48% and seizure-free rate was 28%. SIGNIFICANCE: Across a large, treatment-resistant population, add-on perampanel was retained for ≥1 year by 48% of individuals, and 9% were seizure-free for ≥6 months. TEAEs were in line with previous reports in routine clinical use, and less frequent than in the clinical trial setting. No new or unexpected TEAEs were seen. Despite the limitations of observational studies, our data indicate that some individuals may derive a marked benefit from the use of perampanel.

Metal-Foam-Based Ultrafast Electronucleation of Hydrates at Low Voltages.

The induction time for the nucleation of hydrates can be significantly reduced by electronucleation, which consists of applying an electrical potential across the hydrate precursor solution. This study reveals that open-cell aluminum foam electrodes can reduce the electronucleation induction time by 150× when compared to nonfoam electrodes. Experiments with tetrahydrofuran hydrates show that aluminum foam electrodes trigger near-instantaneous nucleation (in only tens of seconds) at low voltages. Furthermore, this study suggests that two distinct interfacial mechanisms influence electronucleation, namely, electrolytic bubble generation and the formation of metal ion complex-based coordination compounds. These mechanisms (which depend on the electrode material and polarity) affect the induction time to vastly different extents. Coordination compound formation (verified via detection of metal ions in solution) exerts a much greater influence on electronucleation than the mechanistic effects associated with bubble generation. This work uncovers the benefits of using foams to promote electronucleation and shows that foams lead to more deterministic (as opposed to stochastic) nucleation when compared with nonfoam electrodes.

Thalamo-Cortical Disruption Contributes to Short-Term Memory Deficits in Patients with Medial Temporal Lobe Damage.

Short-term (STM) and long-term memory (LTM) have largely been considered as separate brain systems reflecting fronto-parietal and medial temporal lobe (MTL) functions, respectively. This functional dichotomy has been called into question by evidence of deficits on aspects of working memory in patients with MTL damage, suggesting a potentially direct hippocampal contribution to STM. As the hippocampus has direct anatomical connections with the thalamus, we tested the hypothesis that damage to thalamic nuclei regulating cortico-cortical interactions may contribute to STM deficits in patients with hippocampal dysfunction. We used diffusion-weighted magnetic resonance imaging-based tractography to identify anatomical subdivisions in patients with MTL epilepsy. From these, we measured resting-state functional connectivity with detailed cortical divisions of the frontal, temporal, and parietal lobes. Whereas thalamo-temporal functional connectivity reflected LTM performance, thalamo-prefrontal functional connectivity specifically predicted STM performance. Notably, patients with hippocampal volume loss showed thalamic volume loss, most prominent in the pulvinar region, not detected in patients with normal hippocampal volumes. Aberrant thalamo-cortical connectivity in the epileptic hemisphere was mirrored in a loss of behavioral association with STM performance specifically in patients with hippocampal atrophy. These findings identify thalamo-cortical disruption as a potential mechanism contributing to STM deficits in the context of MTL damage.

Aberrant functional connectivity in dissociable hippocampal networks is associated with deficits in memory.

In the healthy human brain, evidence for dissociable memory networks along the anterior-posterior axis of the hippocampus suggests that this structure may not function as a unitary entity. Failure to consider these functional divisions may explain diverging results among studies of memory adaptation in disease. Using task-based and resting functional MRI, we show that chronic seizures disrupting the anterior medial temporal lobe (MTL) preserve anterior and posterior hippocampal-cortical dissociations, but alter signaling between these and other key brain regions. During performance of a memory encoding task, we found reduced neural activity in human patients with unilateral temporal lobe epilepsy relative to age-matched healthy controls, but no upregulation of fMRI signal in unaffected hippocampal subregions. Instead, patients showed aberrant resting fMRI connectivity within anterior and posterior hippocampal-cortical networks, which was associated with memory decline, distinguishing memory-intact from memory-impaired patients. Our results highlight a critical role for intact hippocampo-cortical functional communication in memory and provide evidence that chronic injury-induced functional reorganization in the diseased MTL is behavioral inefficient.

Electrofreezing of water droplets under electrowetting fields.

Electrofreezing is the electrically induced nucleation of ice from supercooled water. This work studies ice nucleation in electrowetted water droplets, wherein there is no electric field inside the droplet resting on a dielectric layer. Instead, there is an interfacial electric field and charge buildup at the solid-liquid interface. This situation is in contrast to most previous electrofreezing studies, which have used bare electrodes, involve current flow, and have a volumetric electric field inside the liquid. Infrared and high-speed visualizations of static water droplets are used to analyze surface electrofreezing. Ultrahigh electric fields of up to 80 V/µm are applied, which is one order of magnitude higher than in previous studies. The results facilitate an in-depth understanding of various mechanisms underlying electrofreezing. First, it is seen that interfacial electric fields alone can significantly elevate freezing temperatures by more than 15 °C, in the absence of current flow. Second, the magnitude of electrofreezing induced temperature elevation saturates at high electric field strengths. Third, the polarity of the interfacial charge does not significantly influence electrofreezing. Overall, it is seen that electrofreezing nucleation kinetics is primarily influenced by the three-phase boundary and not the solid-liquid interface. Through careful electrofreezing measurements on dielectric layers with pinholes to allow current flow, the individual role of electric fields and electric currents on electrofreezing is isolated. It is seen that both the electric field and the electric current influence electrofreezing; however, the physical mechanisms are very different.

Informing Digital Programs for Lupus Self-Management Education: A Systematic Scoping Review.

OBJECTIVE: We describe the characteristics, content, and effectiveness of digital self-management (SM) education programs for lupus and other chronic conditions to identify gaps and inform the improvement of future programs in lupus. METHODS: Three bibliographic databases were searched for articles published between May 2012 and April 2022. The search was cast to capture the breadth of digital SM education programs in the following conditions: lupus, epilepsy, fibromyalgia, multiple sclerosis, sickle cell anemia, Sjögren syndrome, psoriatic arthritis, and rheumatoid arthritis. Title and abstract screening, as well as full-text review, was conducted by two independent reviewers. Data extraction was first completed by one author charting all studies and then, a second time, by four members of the research team charting collaboratively. RESULTS: Of the 1,969 articles identified through the search, 14 met inclusion criteria. Two additional articles were included following bibliography review. The 16 articles represented 12 unique digital SM education programs. Programs covered five conditions: epilepsy (n = 3), fibromyalgia (n = 2), multiple sclerosis (n = 4), lupus (n = 1), and rheumatoid arthritis (n = 2). Most programs were asynchronous and internet-based (n = 9) with a prescribed sequence of content (n = 8). Peer, technical, or specialist support was offered in seven programs. Most programs demonstrated statistically significant improvement of symptoms in the intervention group (n = 8). CONCLUSION: This scoping review summarizes the current landscape for digital SM education programs in lupus and similar conditions. In lupus, further investigation will fill in the gaps around digital SM education needs, user experience, and evaluation of outcomes.

Improved cognitive outcomes with endovascular coiling of ruptured intracranial aneurysms: neuropsychological outcomes from the International Subarachnoid Aneurysm Trial (ISAT).

BACKGROUND AND PURPOSE: The International Subarachnoid Aneurysm Trial (ISAT) reported lower rates of death and disability with endovascular versus neurosurgical treatment of ruptured intracranial aneurysms. However, assessment of functional outcome was limited to the modified Rankin Scale, which is known to be insensitive to cognitive function. A neuropsychological substudy (N-ISAT) was therefore done in all recruits from 8 ISAT centers in the United Kingdom. METHODS: Detailed neuropsychological assessment was performed at a 12-month follow-up visit. Impairment was defined as performance below the 5th percentile of the study population on at least 2 tests in >or=2 major cognitive domains. Analysis was restricted to patients who were not known to be otherwise disabled according to the modified Rankin Scale (ie, modified Rankin Scale 0 to 2). RESULTS: Of 836 patients randomized in ISAT in the 8 UK centers (411 allocated endovascular treatment versus 425 neurosurgery), 224 were dead or disabled before 12-month follow-up (78 allocated endovascular treatment versus 135 neurosurgery). Of the remaining 612 patients eligible for neuropsychological assessment, 137 (65 allocated endovascular treatment versus 72 neurosurgery) did not attend. Of the 474 nondisabled patients who were assessed, 152 (32.1%) had cognitive impairment. Patients with cognitive impairment had reduced self-reported health-related quality of life (P<0.001) in both treatment groups, but cognitive impairment was less common in those allocated endovascular treatment (70 of 262 versus 82 of 212 allocated neurosurgery, OR=0.58, 95% CI 0.38 to 0.87, P=0.0055). The incidence of epilepsy was also lower in the N-ISAT endovascular group (7 versus 18, OR=0.30, 0.11 to 0.77, P=0.005) but was independent of the effect on cognitive function. CONCLUSIONS: Cognitive impairment occurred in approximately one third of patients who were not otherwise disabled according to the modified Rankin Scale in N-ISAT and was more frequent in the neurosurgery group. These results have implications for management of ruptured intracranial aneurysms and more generally for interpretation of the outcomes of clinical trials that use the modified Rankin Scale.

Functional and structural changes in the memory network associated with left temporal lobe epilepsy.

Understanding functional plasticity in memory networks associated with temporal lobe epilepsy (TLE) is central to predicting memory decline following surgery. However, the extent of functional reorganization within memory networks remains unclear. In this preliminary study, we used novel analysis methods assessing network-level changes across the brain during memory task performance in patients with TLE to test the hypothesis that hippocampal functions may not readily shift between hemispheres, but instead may show altered intra-hemispheric organization with unilateral damage. In addition, we wished to relate functional differences to structural changes along specific fibre pathways associated with memory function. Nine pre-operative patients with intractable left TLE and 10 healthy controls underwent functional MRI during complex scene encoding. Diffusion tensor imaging was additionally performed in the same patients. In our study, we found no evidence of inter-hemispheric shifts in memory-related activity in TLE using standard general linear model analysis. However, tensor independent component analysis revealed significant reductions in functional connectivity between bilateral MTL, occipital and left orbitofrontal regions among others in left TLE. This altered orbitofrontal activity was directly related to measures of fornix tract coherence in patients (P < 0.05). Our results suggest that specific fibre pathways, potentially affected by MTL neurodegeneration, may play a central role in functional plasticity in TLE and highlight the importance of network-based analysis approaches. Relative to standard model-based methods, novel objective functional connectivity analyses may offer improved sensitivity to subtle changes in the distribution of memory functions relevant for surgical planning in TLE.

LXR-inverse agonism stimulates immune-mediated tumor destruction by enhancing CD8 T-cell activity in triple negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype that is untreatable with hormonal or HER2-targeted therapies and is also typically unresponsive to checkpoint-blockade immunotherapy. Within the tumor microenvironment dysregulated immune cell metabolism has emerged as a key mechanism of tumor immune-evasion. We have discovered that the Liver-X-Receptors (LXRα and LXRß), nuclear receptors known to regulate lipid metabolism and tumor-immune interaction, are highly activated in TNBC tumor associated myeloid cells. We therefore theorized that inhibiting LXR would induce immune-mediated TNBC-tumor clearance. Here we show that pharmacological inhibition of LXR activity induces tumor destruction primarily through stimulation of CD8+ T-cell cytotoxic activity and mitochondrial metabolism. Our results imply that LXR inverse agonists may be a promising new class of TNBC immunotherapies.

Incidental findings in pediatric research.

The approach to incidental research findings in children emerges by considering the child-parent relationship and balancing divergent interests and preferences. Incidental findings with clear and proximate clinical importance should be disclosed to both. We recommend that particularly sensitive or private information (e.g., pregnancy or drug use) should be disclosed to the adolescent first, while particularly serious information (e.g., cancer) should first be disclosed to the parent. These approaches allow the researcher to form an alliance with one party prior to engaging the other. However, unlike clinical settings, where there may be presumptive expectations of confidentiality about sharing information within the family, in most research settings it is reasonable to plan to disclose such information to both parties. It is important to communicate this plan during the informed consent process separately to adolescents to avoid enrolling adolescents when sensitive incidental findings such as pregnancy and drug use may be detected. The approach to incidental findings without clear and proximate benefit is challenging. Researchers should plan more limited disclosure of such incidental findings for pediatric participants than for adult participants.

Risk and Protective Factors Associated with Surgical Infections among Spine Patients.

BACKGROUND: The purpose of the study was to identify patient-specific and procedure-specific risk and protective factors associated with post-operative surgical site infections (SSIs) among surgical spine patients. METHODS: CINAHL, PubMed, Ovid, Medline, and EBSCO databases were searched for articles within the past 10 years (January 2003-March 2015). The keywords and combinations used in the search included: Spine surgery, post-operative infection, risk factors, orthopedic infections. The search resulted in 842 articles of which 29 met inclusion criteria. This systematic review adheres to preferred reporting items for systematic reviews and meta-analyses guidelines. RESULTS: Evidence about patient-specific and procedure-specific factors associated with increased risk of post-operative SSIs among patients undergoing orthopedic spinal surgery is inconclusive. Gender (male), age, body mass index, cigarette smoking, diabetes mellitus, a history of infection and alcohol abuse were identified as common patient-specific risk factors. Blood transfusion, implantation, and steroid use were found to increase SSIs in certain studies and associated with no significant difference in other studies. Protective factors include the implementation of pre-operative elements to reduce infection; protocols addressing patient-related factors (smoking, weight, glucose) and operation-related factors (antibiotic prophylaxis, prosthetics, length of operation, and pre-operative cultures); incision drains placed intra-operatively; anterior approach; laminar-flow operating theater, and skin antisepsis using chlorhexidine. CONCLUSIONS: Interventions focusing on minimizing patient-specific risk factors and operation-specific risk factors and optimizing patient-specific protective factors and operation-specific protective factors are most effective in minimizing the likelihood of a post-operative infection among patients undergoing orthopedic spinal surgical procedures. The studies reviewed provide conflicting evidence relative to risk and protective factors.

Rev-Erb co-regulates muscle regeneration via tethered interaction with the NF-Y cistrome.

OBJECTIVE: The loss of skeletal muscle mass and strength are a central feature of traumatic injury and degenerative myopathies. Unfortunately, pharmacological interventions typically fail to stem the long-term decline in quality of life. Reduced Rev-Erb-mediated gene suppression in cultured C2C12 myoblasts has been shown to stimulate myoblast differentiation. Yet the mechanisms that allow Rev-Erb to pleiotropically inhibit muscle differentiation are not well understood. In this study, we sought to elucidate the role of Rev-Erb in the regulation of muscle differentiation and regeneration in vivo. METHODS: Using Rev-Erbα/ß shRNAs, pharmacological ligands, and Rev-Erbα null and heterozygous mice, we probed the mechanism of Rev-Erbα/ß regulation of muscle differentiation and muscle regeneration. RESULTS: ChIP seq analysis of Rev-Erb in differentiating myoblasts showed that Rev-Erbα did not transcriptionally regulate muscle differentiation through cognate Rev-Erb/ROR-response elements but through possible interaction with the cell fate regulator NF-Y at CCAAT-motifs. Muscle differentiation is stimulated by Rev-Erb release from CCAAT-motifs at promoter and enhancer elements of a number of myogenesis proteins. Partial loss of Rev-Erb expression in mice heterozygous for Rev-Erbα accelerated muscle repair in vivo whereas Rev-Erb knockout mice showed deficiencies in regenerative repair compared to wild type mice. These phenotypic differences between heterozygous and knockout mice were not apparently dependent on MRF induction in response to injury. Similarly, pharmacological disruption of Rev-Erb suppressive activity in injured muscle accelerated regenerative repair in response to acute injury. CONCLUSIONS: Disrupting Rev-Erb activity in injured muscle accelerates regenerative muscle repair/differentiation through transcriptional de-repression of myogenic programs. Rev-Erb, therefore, may be a potent therapeutic target for a myriad of muscular disorders.

Electronucleation for Rapid and Controlled Formation of Hydrates.

Nucleation of hydrates involves very long induction times (hours to days), which is a challenge for applications requiring rapid hydrate formation. This study introduces and analyzes the use of electric fields to accelerate and control hydrate nucleation. Experiments with tetrahydrofuran (THF) hydrates reveal that the induction time can be reduced by 100×, by applying an electrical potential across the precursor solution. The induction time rapidly decreases with increasing voltages and is on the order of a few minutes at 100 V. It is seen that voltage-induced current flow in the solution is responsible for electronucleation. Very low currents (microamperes) are sufficient for electronucleation. Nucleation promotion can be attributed to phenomena associated with bubble formation due to chemical reactions at the electrodes. Overall, this study lays the foundation for the control and promotion of nucleation by electric fields, and enables possibilities for instantaneous nucleation.

Determining high touch areas in the operating room with levels of contamination.

BACKGROUND: The Centers for Disease Control and Prevention put forth the recommendation to clean areas considered high touch more frequently than minimal touch surfaces. The operating room was not included in these recommendations. The purpose of this study was to determine the most frequently touched surfaces in the operating room and their level of contamination. METHODS: Phase 1 was a descriptive study to identify high touch areas in the operating room. In phase 2, high touch areas determined in phase 1 were cultured to determine if high touch areas observed were also highly contaminated and if they were more contaminated than a low touch surface. RESULTS: The 5 primary high touch surfaces in order were the anesthesia computer mouse, OR bed, nurse computer mouse, OR door, and anesthesia medical cart. Using the OR light as a control, this study demonstrated that a low touch area was less contaminated than the high touch areas with the exception of the OR bed. CONCLUSIONS: Based on information and data collected in this study, it is recommended that an enhanced cleaning protocol be established based on the most frequently touched surfaces in the operating room.

Crew Resource Management for Obstetric and Neonatal Teams to Improve Communication During Cesarean Births.

OBJECTIVE: To assess the effectiveness of crew resource management training and interventions on the quality and quantity of communication during cesarean births in a tertiary academic hospital's labor and birthing services. DESIGN: A prospective pre-post crew resource management training intervention. SETTING: Tertiary academic hospital in the Western United States. PARTICIPANTS: All members of obstetric and neonatal teams that participated in cesarean births. METHODS: Over a 5-month time period, all obstetric and neonatal staff were required to participate in team training in crew resource management critical language, communication, and team structure. Trained observers collected baseline data (n = 52) for 3 months on the quantity and quality of communications that occurred during cesarean births. Postintervention data (n = 50) were gathered for 3 months after team training. Analysis approach included use of Fisher's exact test, independent-samples t test, and multilevel generalized linear regression models with Poisson distribution. RESULTS: There was a statistically significant increase in quantity and quality of communication from pre- to postintervention assessment for obstetric and neonatal staff. Although the increase in quality was similarly great between both types of teams, increase in quantity was more substantial in obstetric staff. CONCLUSION: Principles of team communication training shown to be effective in increasing communication among team members in a variety of clinical areas were also effective in improving communication in the labor and birth setting during cesarean births.

Saltwater icephobicity: Influence of surface chemistry on saltwater icing.

Most studies on icephobicity focus on ice formation with pure water. This manuscript presents studies to understand the influence of surfaces on saltwater ice nucleation and propagation. Experiments are conducted to quantify the influence of surface chemistry on saltwater ice nucleation and to understand the utility of superhydrophobic surfaces for saltwater icephobicity. These experiments are conducted with pure water and two sodium chloride solutions, which represent the salinity of seawater and briny produced water. It is seen that the presence of salt slows down the ice front propagation velocity significantly. Saltwater droplet impact dynamics on superhydrophobic surfaces are also different from pure water. Saltwater droplets retract more and a greater fraction of impacting liquid is repelled from the superhydrophobic surface. It is seen that the greater bounciness of saltwater droplets is a result of slower ice nucleation propagation kinetics. These experiments indicate that superhydrophobic surfaces will have better resistance to impact icing with saltwater than pure water and can remain useful at temperatures as low as -40 °C. Overall, this work is a starting point for further studies on heterogeneous nucleation in saltwater and serves as a bridge between the widely studied freshwater icephobic surfaces and saltwater-related applications.

Evaluating the Clinical Utility of the Medical Symptom Validity Test (MSVT): A Clinical Series.

Performance validity tests (PVTs) are not widely used beyond medico-legal contexts in the UK. A UK survey suggests clinicians have reservations about their accuracy in clinical settings. This study sought to explore the validity of PVTs in an acute adult neuropsychology setting and to establish a potential "false positive" (FP) base rate. Failures on the Medical Symptom Validity Test (MSVT) in a consecutive clinical series of 405 patients were evaluated systematically and allocated to groups depending on clinical context. All failures were checked against the test's "dementia profile". Of the 405 participants, 329 passed the MSVT (81.2%), while 76 participants (18.8%) failed based on standard criteria. A 5.2% rate of potentially 'unexplained' failures was found. Other reasons for failure were classified as: presumed malingered neurocognitive dysfunction (4.6%), dementia/significant cognitive impairment (3.7%), technical/visual problems (1.8%), and "unexplained failure" with contributory factors (2.4%). These results suggest test specificity between 0.95 and 0.90. Most of the clinically significantly impaired patients matched the dementia profile (86.7%). Our results support the sensitivity, but not the specificity, of the dementia profile. However, approximately 1 in 20 patients failed the MSVT despite an otherwise unremarkable neuropsychological presentation; moreover, mood and pain may affect MSVT performance. Clinical implications for interpreting test scores are discussed.

High efficiency creation of human monoclonal antibody-producing hybridomas.

The native human antibody repertoire holds unexplored potential for the development of novel monoclonal antibody therapeutics. Current techniques that fuse immortal cells and primary B-lymphocytes are sub-optimal for the routine production of hybridomas that secrete human monoclonal antibodies. We have found that a murine cell line that ectopically expresses murine interleukin-6 (mIL-6) and human telomerase (hTERT) efficiently forms stable human antibody-secreting heterohybridomas through cell fusion with primary human B-lymphocytes. The hybrid cells maintain secretion of human antibodies derived from the primary B-lymphocytes through multiple rounds of cloning. Using splenic B-lymphocytes from a patient immunized with a Streptococcus pneumoniae capsular polysaccharide vaccine, we have succeeded in creating hybridomas that secrete human monoclonal antibodies specific for S. pneumoniae antigens. Using peripheral blood lymphocytes, we have similarly cloned a human antibody that binds a viral antigen. These experiments establish that SP2/0-derived cell lines ectopically expressing mIL-6 and hTERT will enable the rapid cloning of native human monoclonal antibodies.

Effects of GCP-II inhibition on responses of dorsal horn neurones after inflammation and neuropathy: an electrophysiological study in the rat.

N-Acetylaspartylglutamate (NAAG) is a peptide neurotransmitter present in the brain and spinal cord. It is hydrolysed by glutamate carboxypeptidase II (GCPII); thus, the GCP-II inhibitor 2-[phosphono-methyl]-pentanedioic acid (2-PMPA) protects endogenous NAAG from degradation, allowing its effects to be studied in vivo. We recorded the effect of spinal 2-PMPA (50-1000 microg) on the electrical-evoked activity of dorsal horn neurones in normal and carrageenan-inflamed animals, and in the spinal nerve ligation (SNL) model of neuropathy and sham-operated animals. In normal animals, 1000 microg 2-PMPA selectively inhibited noxious-evoked activity (input, post-discharge and C- and Adelta-fibre-evoked responses), and not low threshold Abeta-fibre-evoked responses. After carrageenan inflammation, the lower dose of 100 microg 2-PMPA inhibited input, post-discharge, C- and Adelta-fibre-evoked responses by a significantly greater amount than the same dose in normal animals. 2-PMPA inhibited neuronal responses less consistently in sham-operated and SNL animals, and effects were not significantly different from those seen in normal animals. NAAG is an agonist at the inhibitory metabotropic glutamate receptor mGluR3, and 2-PMPA may inhibit nociceptive transmission in normal animals by elevating synaptic NAAG levels, allowing it to activate mGluR3 and thus reducing transmitter release from afferent nerve terminals. mGluR3 expression in the superficial dorsal horn is upregulated after peripheral inflammation, perhaps explaining the greater inhibition of neuronal responses we observed after carrageenan inflammation. These results support an important role of endogenous NAAG in the spinal processing of noxious information.

Coaching to improve the quality of communication during briefings and debriefings.

Communication breakdowns have been identified as a root cause of many medical errors. Sentinel events occurring in surgery comprise a significant number of these events. Despite the addition of briefings and debriefings in the OR and the introduction of crew resource management principles, communication problems continue to occur in the surgical setting. The purpose of this research was to evaluate coaching as an intervention to improve the quality of OR briefings and debriefings. A retired orthopedic surgeon conducted coaching that included all members of the perioperative team. The quality of both briefings and debriefings significantly improved after the coaching intervention. Analysis of the results of this study suggests that coaching should be considered as an intervention to improve communication during surgical procedures, especially during briefings and debriefings.