An Uncommon Diagnosis in a Child Presenting With Double Vision and Imbalance.

Acute disseminated encephalomyelitis (ADEM) is exceptionally uncommon, with approximately 3 pediatric cases reported in the United States each year. Given the uncommon nature of ADEM, most of the current data rely heavily on case reports. The overwhelming majority of cases have been reported after an acute viral infection or vaccination. Although up to 90% of cases exhibit full remission after intravenous steroids, those in which treatment is delayed can display debilitating sequelae. Here, we present a case of ADEM in a 7-year-old boy who presented with double vision and imbalance with no recent history of acute viral infections or vaccinations.

The Relationship Between Grit, Burnout, and Well-being in Emergency Medicine Residents.

BACKGROUND: Burnout has become endemic in medicine, across all specialties and levels of training. Grit, defined as "perseverance and passion for long-term goals," attempts to quantify the ability to maintain sustained effort throughout an extended length of time. Our objective is to assess burnout and well-being and examine their relationship with the character trait, grit, in emergency medicine residents. METHODS: In Fall 2016, we conducted a multicenter cross-sectional survey at five large, urban, academically affiliated emergency departments. Residents were invited to anonymously provide responses to three validated survey instruments; the Short Grit Scale, the Maslach Burnout Inventory, and the World Health Organization-5 Well-Being Index. RESULTS: A total of 222 residents completed the survey (response rate = 86%). A total of 173 residents (77.9%) met criteria for burnout and 107 residents (48.2%) met criteria for low well-being. Residents meeting criteria for burnout and low well-being had significantly lower mean grit scores than those that did not meet criteria. Residents with high grit scores had lower odds of experiencing burnout and low well-being (odds ratio [OR] = 0.26, 95% confidence interval [CI] = 0.46-0.85; and [OR] = 0.33, 95% CI = 0.16-0.72, respectively). Residents with low grit scores were more likely to experience burnout and more likely to have low well-being (OR = 6.17, 95% CI = 1.43-26.64; and OR = 2.76, 95% CI = 1.31-5.79, respectively). CONCLUSION: A significant relationship exists between grit, burnout, and well-being. Residents with high grit appear to be less likely to experience burnout and low well-being while those with low grit are more likely to experience burnout and low well-being.

Using an alumni survey to target improvements in an emergency medicine training programme.

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) is the governing body responsible for accrediting graduate medical training programme in the USA. The Emergency Medicine Milestones (EM-Milestones) were developed by the ACGME and American Board of Emergency Medicine as a guide and monitoring tool for the knowledge, skills, abilities and experiences to be acquired during training. Alumni surveys have been reported as a valuable resource for training programme to identify areas for improvement; however, there are few studies regarding programme improvement in emergency medicine. We aimed to use the EM-Milestones, adapted as an alumni self-assessment survey, to identify areas for training programme improvement. METHODS: This study was conducted at an urban, academic affiliated, community hospital in New York city with an emergency medicine training programme consisting of 30 residents over 3 years. Alumni of our emergency medicine training programme were sent an EM-Milestones-based self-assessment survey. Participants evaluated their ability in each EM-Milestones subcompetency on a Likert scale. Data were analysed using descriptive statistics. RESULTS: Response rate was 74% (69/93). Alumni reported achieving the target performance in 5/6 general competencies, with Systems-Based Practice falling below the target performance. The survey further identified 6/23 subcompetencies (Pharmacotherapy, Ultrasound, Wound Management, Patient Safety, Systems-Based Management and Technology) falling below the target performance level. DISCUSSION: Alumni self-evaluation of competence using the EM-Milestones provides valuable information concerning confidence to practice independently; these data, coupled with regular milestone evaluation of existing trainees, can identify problem areas and provide a blueprint for targeted programme improvement.

Progressive Disordered Movements in an Infant Leads to Rare Diagnosis.

Desmoplastic infantile ganglioglioma (DIG) is a supratentorial superficially-located cystic neuroepithelial tumor. It is an exceedingly rare tumor with an incidence of <0.1% of central nervous tumors; approximately 60 cases have been reported in the literature. We present a case of a three-month-old infant with progressive disordered movements described as intermittent upper body stiffening with associated eye blinking, drooling, and change in level of alertness. A seizure was witnessed in the emergency department, after which the child was sent for imaging studies. Magnetic resonance imaging (MRI) revealed a large solid and cystic mass in the temporal region measuring 8.6cm × 7.9cm × 5.1cm. The infant underwent complete surgical resection, and post-surgical pathology revealed a diagnosis of DIG. The patient had an excellent post-operative course in the months following discharge. At his last well-child visit, no neurological deficits were appreciated and the infant was meeting expected milestones for his age.

Induction of mitochondrial biogenesis protects against caspase-dependent and caspase-independent apoptosis in L6 myoblasts.

Apoptotic signaling plays an important role in skeletal muscle degradation, atrophy, and dysfunction. Mitochondria are central executers of apoptosis by directly participating in caspase-dependent and caspase-independent cell death signaling. Given the important apoptotic role of mitochondria, altering mitochondrial content could influence apoptosis. Therefore, we examined the direct effect of modest, but physiological increases in mitochondrial biogenesis and content on skeletal muscle apoptosis using a cell culture approach. Treatment of L6 myoblasts with SNAP or AICAR (5h/day for 5days) significantly increased PGC-1, AIF, cytochrome c, and MnSOD protein content as well as MitoTracker staining. Following induction of mitochondrial biogenesis, L6 myoblasts displayed decreased sensitivity to apoptotic cell death as well as reduced caspase-3 and caspase-9 activation following exposure to staurosporine (STS) and C2-ceramide. L6 myoblasts with higher mitochondrial content also exhibited reduced apoptosis and AIF release following exposure to hydrogen peroxide (H2O2). Analysis of several key apoptosis regulatory proteins (ARC, Bax, Bcl-2, XIAP), antioxidant proteins (catalase, MnSOD, CuZnSOD), and reactive oxygen species (ROS) measures (DCF and MitoSOX fluorescence) revealed that these mechanisms were not responsible for the observed cellular protection. However, myoblasts with higher mitochondrial content were less sensitive to Ca(2+)-induced mitochondrial permeability transition pore formation (mPTP) and mitochondrial membrane depolarization. Collectively, these data demonstrate that increased mitochondrial content at physiological levels provides protection against apoptotic cell death by decreasing caspase-dependent and caspase-independent signaling through influencing mitochondrial Ca(2+)-mediated apoptotic events. Therefore, increasing mitochondrial biogenesis/content may represent a potential therapeutic approach in skeletal muscle disorders displaying increased apoptosis.

Elevated skeletal muscle apoptotic signaling following glutathione depletion.

Oxidative stress has a well-established role in numerous intracellular signaling pathways, including apoptosis. Glutathione is an important cellular antioxidant and is the most abundant low molecular weight thiol in the cell. Although previous work has shown a link between glutathione and apoptosis, this relationship has not been defined in skeletal muscle. The present investigation examined the effect of glutathione depletion on skeletal muscle apoptotic signaling, and mitochondrial apoptotic-susceptibility. Administration of L: -buthionine-[S,R]-sulfoximine (BSO; 30 mM in drinking water for 10 days) caused glutathione depletion in whole muscle and isolated mitochondria, as well as elevated muscle catalase protein content and reactive oxygen species (ROS) generation. Glutathione depletion was associated with elevated DNA fragmentation, mitochondrial Bax levels, Poly(ADP-ribose) polymerase (PARP) cleavage, and calpain activity; however, caspase-3, -8, and -9 activity were not altered. BSO administration was also associated with higher cytosolic and nuclear protein levels of apoptosis-inducing factor (AIF), but not cytochrome c, second mitochondria-derived activator of caspase (Smac), or endonuclease G (EndoG). In addition, isolated mitochondria from BSO animals demonstrated significantly lower membrane potential, increased Ca(2+)-induced permeability transition pore opening, and greater basal and ROS-induced AIF and cytochrome c release. These results demonstrate that glutathione depletion in skeletal muscle increases caspase-independent signaling, as well as augments mitochondrial-associated apoptotic events to subsequent cell death stimuli.

FAT/CD36 is located on the outer mitochondrial membrane, upstream of long-chain acyl-CoA synthetase, and regulates palmitate oxidation.

FAT/CD36 (fatty acid translocase/Cluster of Differentiation 36), a plasma membrane fatty-acid transport protein, has been found on mitochondrial membranes; however, it remains unclear where FAT/CD36 resides on this organelle or its functional role within mitochondria. In the present study, we demonstrate, using several different approaches, that in skeletal muscle FAT/CD36 resides on the OMM (outer mitochondrial membrane). To determine the functional role of mitochondrial FAT/CD36 in this tissue, we determined oxygen consumption rates in permeabilized muscle fibres in WT (wild-type) and FAT/CD36-KO (knockout) mice using a variety of substrates. Despite comparable muscle mitochondrial content, as assessed by unaltered mtDNA (mitochondrial DNA), citrate synthase, ß-hydroxyacyl-CoA dehydrogenase, cytochrome c oxidase complex IV and respiratory capacities [maximal OXPHOS (oxidative phosphorylation) respiration] in WT and KO mice, palmitate-supported respiration was 34% lower in KO animals. In contrast, palmitoyl-CoA-supported respiration was unchanged. These results indicate that FAT/CD36 is key for palmitate-supported respiration. Therefore we propose a working model of mitochondrial fatty-acid transport, in which FAT/CD36 is positioned on the OMM, upstream of long-chain acyl-CoA synthetase, thereby contributing to the regulation of mitochondrial fatty-acid transport. We further support this model by providing evidence that FAT/CD36 is not located in mitochondrial contact sites, and therefore does not directly interact with carnitine palmitoyltransferase-I as original proposed.