Turmeric-Associated Liver Injury: A Rare Case of Drug-Induced Liver Injury.

Turmeric is popularly used as a naturopathic supplement associated with myriad benefits and has long been generally regarded as safe. However, increasing reports of turmeric-associated liver injury have emerged over recent years. This case presents a female patient without significant past medical history who presents with signs and symptoms of acute hepatitis after consuming a turmeric-containing tea. Her case adds to a growing body of evidence that dosage safety, manufacturing, and pharmacologic delivery practices for turmeric supplements should be investigated.

Established and Emerging Therapies in Acute Spinal Cord Injury.

Acute spinal cord injury (SCI) is devastating for patients and their caretakers and has an annual incidence of 20-50 per million people. Following initial assessment with appropriate physical examination and imaging, patients who are deemed surgical candidates should undergo decompression with stabilization. Earlier intervention can improve neurological recovery in the post-operative period while allowing earlier mobilization. Optimized medical management is paramount to improve outcomes. Emerging strategies for managing SCI in the acute period stem from an evolving understanding of the pathophysiology of the injury. General areas of focus include ischemia prevention, reduction of secondary injury due to inflammation, modulation of the cytotoxic and immune response, and promotion of cellular regeneration. In this article, we review established, emerging, and novel experimental therapies. Continued translational research on these methods will improve the feasibility of bench-to-bedside innovations in treating patients with acute SCI.

Firearm-Related Pediatric Head Trauma: A Scoping Review.

BACKGROUND: Firearm-related injury is a significant cause of morbidity and mortality in pediatric populations. Despite a disproportionate role in the most morbid outcomes in both traumatic brain injury and firearm-related injury populations, firearm-related traumatic brain injury (frTBI) is an understudied epidemiological entity. There is need to increase understanding and promote interventions that reduce this burden of disease. OBJECTIVE: To assess the evidence characterizing pediatric frTBI to highlight trends and gaps regarding burden of disease and interventions to reduce frTBI. METHODS: We conducted a scoping review under Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Scoping Review (PRISMA-ScR) guidelines on peer-reviewed studies across 5 databases (Medline OVID, EMBASE, Web of Science Legal Collection, PsychINFO, and Academic Search Complete). English studies examining pediatric frTBI epidemiology, prevention, and/or social or legal policy advocacy were included. Articles were excluded if they more generally discussed pediatric firearm-related injury without specific analysis of frTBI. RESULTS: Six studies satisfied inclusion criteria after screening and full-text assessment. Limited studies specifically addressed the burden of disease caused by frTBI. There was an increased risk for both injury and death from frTBI in men, preteenage and teenage youths, minorities, and individuals in firearm-owning households. Further study is required to ascertain if suggested methods of targeted patient screening, firearm-injury prevention counseling, and advocacy of safety-oriented policy tangibly affect rates or outcomes of pediatric frTBI. CONCLUSION: By understanding published epidemiological data and areas of intervention shown to reduce frTBIs, neurosurgeons can become further engaged in public health and prevention rather than strictly treatment after injury.

Predictive value of magnetoencephalography in guiding the intracranial implant strategy for intractable epilepsy.

OBJECTIVE: Magnetoencephalography (MEG) is a useful component of the presurgical evaluation of patients with epilepsy. Due to its high spatiotemporal resolution, MEG often provides additional information to the clinician when forming hypotheses about the epileptogenic zone (EZ). Because of the increasing utilization of stereo-electroencephalography (sEEG), MEG clusters are used to guide sEEG electrode targeting with increasing frequency. However, there are no predefined features of an MEG cluster that predict ictal activity. This study aims to determine which MEG cluster characteristics are predictive of the EZ. METHODS: The authors retrospectively analyzed all patients who had an MEG study (2017-2021) and underwent subsequent sEEG evaluation. MEG dipoles and sEEG electrodes were reconstructed in the same coordinate space to calculate overlap among individual contacts on electrodes and MEG clusters. MEG cluster features-including number of dipoles, proximity, angle, density, magnitude, confidence parameters, and brain region-were used to predict ictal activity in sEEG. Logistic regression was used to identify important cluster features and to train a binary classifier to predict ictal activity. RESULTS: Across 40 included patients, 196 electrodes (42.2%) sampled MEG clusters. Electrodes that sampled MEG clusters had higher rates of ictal and interictal activity than those that did not sample MEG clusters (ictal 68.4% vs 39.8%, p < 0.001; interictal 71.9% vs 44.6%, p < 0.001). Logistic regression revealed that the number of dipoles (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.04-1.14, t = 3.43) and confidence volume (OR 0.02, 95% CI 0.00-0.86, t = -2.032) were predictive of ictal activity. This model was predictive of ictal activity with 77.3% accuracy (sensitivity = 80%, specificity = 74%, C-statistic = 0.81). Using only the number of dipoles had a predictive accuracy of 75%, whereas a threshold between 14 and 17 dipoles in a cluster detected ictal activity with 75.9%-85.2% sensitivity. CONCLUSIONS: MEG clusters with approximately 14 or more dipoles are strong predictors of ictal activity and may be useful in the preoperative planning of sEEG implantation.

Focal Inflammation Causes Carbenoxolone-Sensitive Tactile Hypersensitivity in Mice.

A focal and transitory inflammation induced by injection of complete Freund's adjuvant (CFA) in the submandibular skin of mice elicits pain behavior that persists for several weeks after the initial inflammation has resolved. Chronic pain, assessed as tactile hypersensitivity to stimulation with von Frey filaments, was evident from 1-7 weeks following CFA injection, although inflammation at the injection site was resolved by 3-4 weeks. In contrast, there were no changes in tactile sensitivity in the paw (un-injected site for comparison), no alterations in open field behavior and no differences in a functional observation battery evident in CFA-treated mice compared to controls (saline-injected) or to baseline (before CFA injection). Neither strain (Balb/c vs. C57BL/6) nor sex differences in baseline tactile threshold were significant in the submandibular skin. CFA-induced tactile hypersensitivity was also not a function of strain or sex. A single intraperitoneal injection of the gap junction blocker carbenoxolone (CBX) restored normal tactile thresholds in CFA-treated mice when administered at the peak of inflammation (1 week), after significant resolution of inflammation (3 weeks) or after total resolution of inflammation (4 and 5 weeks) without altering the tactile threshold of control subjects, tactile threshold in the paw or open field behavior. Thus, in this novel model of post-inflammatory pain, transitory inflammation induced persistent sex- and strain-independent behavioral hypersensitivity that was reversed by the gap junction blocker CBX, suggesting neuronal and/or glial plasticity as a major component of the chronic pain.

The identification a novel, selective, non-steroidal, functional glucocorticoid receptor antagonist.

The identification of novel, potent, non-steroidal/small molecule functional GR antagonist GSK1564023A selective over PR is described. Associated structure-activity relationships and the process of optimisation of an initial HTS hit are also described.

Bidirectional calcium signaling between satellite glial cells and neurons in cultured mouse trigeminal ganglia.

Astrocytes communicate with neurons, endothelial and other glial cells through transmission of intercellular calcium signals. Satellite glial cells (SGCs) in sensory ganglia share several properties with astrocytes, but whether this type of communication occurs between SGCs and sensory neurons has not been explored. In the present work we used cultured neurons and SGCs from mouse trigeminal ganglia to address this question. Focal electrical or mechanical stimulation of single neurons in trigeminal ganglion cultures increased intracellular calcium concentration in these cells and triggered calcium elevations in adjacent glial cells. Similar to neurons, SGCs responded to mechanical stimulation with increase in cytosolic calcium that spread to the adjacent neuron and neighboring glial cells. Calcium signaling from SGCs to neurons and among SGCs was diminished in the presence of the broad-spectrum P2 receptor antagonist suramin (50 muM) or in the presence of the gap junction blocker carbenoxolone (100 muM), whereas signaling from neurons to SGCs was reduced by suramin, but not by carbenoxolone. Following induction of submandibular inflammation by Complete Freund's Adjuvant injection, the amplitude of signaling among SGCs and from SGCs to neuron was increased, whereas the amplitude from neuron to SGCs was reduced. These results indicate for the first time the presence of bidirectional calcium signaling between neurons and SGCs in sensory ganglia cultures, which is mediated by the activation of purinergic P2 receptors, and to some extent by gap junctions. Furthermore, the results indicate that not only sensory neurons, but also SGCs release ATP. This form of intercellular calcium signaling likely plays key roles in the modulation of neuronal activity within sensory ganglia in normal and pathological states.

Cognitive dysfunction in mice infected with Plasmodium berghei strain ANKA.

Cerebral malaria complicated by cognitive sequelae is a major cause of morbidity in humans infected with Plasmodium falciparum. To model cognitive function after malaria, we created a rodent model of cerebral malaria by infecting C57BL/6 mice with Plasmodium berghei strain ANKA. After 7 days, an object-recognition test of working memory revealed a significant impairment in the visual memory of infected mice. This impairment was observed in the absence of confounding effects of infection. The cognitive dysfunction correlated with hemorrhage and inflammation. Furthermore, microglial activity and morphological changes detected throughout the brains of infected mice were absent from the brains of control mice, and this correlated with the measured cognitive defects. Similar testing methods in human studies could help identify subjects at risk for an adverse cognitive outcome. This murine model should facilitate the study of adjunctive methods to ameliorate adverse neurological outcomes in cerebral malaria.