Fulminant myocarditis secondary to murine typhus mimicking acute coronary syndrome.

Myocarditis is a disease with variable clinical presentation, ranging from an uncomplicated febrile illness to cardiogenic shock. Herein, we report a case of fulminant myocarditis secondary to murine typhus in a 52-year-old male that initially mimicked an acute coronary syndrome. Emergent coronary angiography showed angiographically normal coronary arteries. Left ventriculography showed global hypokinesis with an ejection fraction of 10%. The patient required mechanical support with an intra-aortic balloon pump and fully recovered. .

An update on allergic emergencies.

PURPOSE OF REVIEW: To provide an updated framework of management for allergic emergencies. RECENT FINDINGS: The most frequent causes of anaphylaxis include medications, foods, and stinging insects. Early and appropriate administration of epinephrine is critical to managing anaphylaxis. Although epinephrine is well tolerated and there is no absolute contraindication to using epinephrine in first-aid management of anaphylaxis, many patients at risk for anaphylaxis still fail to carry and use the medication prior to seeking emergency care. Outcomes of allergic emergencies can be improved by educational efforts that focus on adherence to emergency plans, as well as asthma controller treatments in patients with persistent asthma. Though venom immunotherapy is known to decrease the risk for stinging insect anaphylaxis, the role of emerging strategies for food allergen immunotherapy in reducing cases of anaphylaxis requires further study. SUMMARY: Fatalities resulting from anaphylaxis and asthma are rare. Patient education serves an important role in preparing for unexpected emergencies, instituting prompt and appropriate treatment, and incorporating effective strategies into the lives of children and families.

FAM81A protein, a novel component of the postsynaptic density in adult brain.

Analysis of affinity-purified PSD-95 complexes had previously identified a 'hypothetical protein', product of the gene FAM81A [1]. The present study examined the tissue and subcellular distribution of FAM81A protein and its expression levels during development. Comparison of different organs indicates selective expression of FAM81A protein in brain. FAM81A is expressed late in development, with a post-natal gradual increase in brain levels that parallels the expression of PSD-95. Comparison of subcellular fractions from adult brain shows that the distribution of FAM81A protein is similar to that of PSD-95, with a drastic enrichment in the postsynaptic density fraction. Immuno-electron microscopy of adult brain tissue reveals specific immunogold labeling for FAM81A protein at postsynaptic densities in the forebrain. The label for FAM81A protein is concentrated at the cytoplasmic edge of the electron-dense core of the postsynaptic density, with a mean distance of ∼33 nm from the postsynaptic membrane. These observations firmly establish FAM81A protein as a component of the postsynaptic density in the adult brain, suggesting a role in synaptic function.

Metachronous Neoplasias Arise in a Higher Proportion of Colon Segments From Which Large Polyps Were Previously Removed, and Can be Used to Estimate Incomplete Resection of 10-20 mm Colorectal Polyps.

BACKGROUND & AIMS: Incomplete resection of polyps could be an important cause of post-colonoscopy colorectal cancer. However, it is difficult to study progression of incompletely removed polyps or their clinical importance. We aimed to estimate incomplete polyp resection using risk of metachronous neoplasia per colon segment. METHODS: We performed a retrospective study of 1031 patients (6186 colon segments) who initially underwent resection of a large (10-20 mm) neoplastic polyp at 2 academic medical centers (from 2000 through 2012) and then underwent a subsequent colonoscopy within 0.5 to 5 years. We determined the proportions of metachronous neoplasia in colon segments from which a single large neoplastic polyp was removed and in segments without prior neoplasia. We then used the absolute difference in proportions between these groups to estimate the rate of incomplete resection. Our analysis assumed that development of metachronous neoplasia in each colon segment was the consequence of a newly grown polyp, a previously missed polyp, or an incompletely removed polyp. RESULTS: Metachronous neoplasia was detected in 177 of 757 segments (23.4%) with a single large polyp, and in 438 of 4232 segments (10.3%) without any neoplasia at baseline colonoscopy (P < .001). Resections were therefore estimated to be incomplete in 13.0% of segments (95% CI, 9.8-16.2). This proportion was greater for sections with non-pedunculated polyps (18.3%; 95% CI, 14.2-22.5) than pedunculated polyps (3.5%; 95% CI, -0.7 to -11.3; P < .001). A higher proportion of piecemeal resections appeared to be incomplete (28.0%; 95% CI, 20.2-35.7) than of en bloc resections (9.2%; 95% CI, 5.9-12.5) (P < .001). No differences in incomplete resection were associated with polyp histology. CONCLUSION: Metachronous neoplasia arises in a significantly higher proportion of colon segments from which a polyp was previously removed. Based on these data, we estimate that 13% of all large polyps are incompletely resected and 18% of large non-pedunculated polyps are incompletely resected. These findings indicate that incomplete resection could be a risk factor for later development of neoplasia. Segment metachronous neoplasia might be used as a marker of resection quality.

IRSp53 accumulates at the postsynaptic density under excitatory conditions.

IRSp53 (BAIAP2) is an abundant protein at the postsynaptic density (PSD) that binds to major PSD scaffolds, PSD-95 and Shanks, as well as to F-actin. The distribution of IRSp53 at the PSD in cultured hippocampal neurons was examined under basal and excitatory conditions by immuno-electron microscopy. Under basal conditions, label for IRSp53 is concentrated at the PSD. Upon depolarization by application of a medium containing 90 mM K+, the intensity of IRSp53 label at the PSD increased by 36±7%. Application of NMDA (50 µM) yielded 53±1% increase in the intensity of IRSp53 label at the PSD compared to controls treated with APV, an NMDA antagonist. The accumulation of IRSp53 label upon application of high K+ or NMDA was prominent at the deeper region of the PSD (the PSD pallium, lying 40-120 nm from the postsynaptic plasma membrane). IRSp53 molecules that accumulate at the distal region of the PSD pallium under excitatory conditions are too far from the plasma membrane to fulfill the generally recognized role of the protein as an effector of membrane-bound small GTPases. Instead, these IRSp53 molecules may have a structural role organizing the Shank scaffold and/or linking the PSD to the actin cytoskeleton.

CaMKII-mediated displacement of AIDA-1 out of the postsynaptic density core.

Ankyrin repeat and sterile alpha motif domain-containing protein 1B (ANKS1B, also known as AIDA-1) is a major component of the postsynaptic density (PSD) in excitatory neurons where it concentrates at the electron-dense core under basal conditions and moves out during activity. This study investigates the molecular mechanism underlying activity-induced displacement of AIDA-1. Experiments with PSD fractions from brain indicate phosphorylation of AIDA-1 upon activation of endogenous CaMKII. Immuno-electron microscopy studies show that treatment of hippocampal neurons with NMDA results in an ~ 30 nm shift in the median distance of the AIDA-1 label from the postsynaptic membrane, an effect that is blocked by the CaMKII inhibitor tatCN21. CaMKII-mediated redistribution of AIDA-1 is similar to that observed for SynGAP. CaMKII-mediated removal of two abundant PSD-95-binding proteins from the PSD core during activity is expected to initiate a molecular reorganization at the PSD.

Zinc Stabilizes Shank3 at the Postsynaptic Density of Hippocampal Synapses.

Shank3 is a postsynaptic density (PSD) scaffold protein of the Shank family. Here we use pre-embedding immunogold electron microscopy to investigate factors influencing the distribution of Shank3 at the PSD. In dissociated rat hippocampal cultures under basal conditions, label for Shank3 was concentrated in a broad layer of the PSD, ~20-80 nm from the postsynaptic membrane. Upon depolarization with high K+ (90 mM, 2 min), or application of NMDA (50 µM, 2 min), both the labeling intensity at the PSD and the median distance of label from the postsynaptic membrane increased significantly, indicating that Shank3 molecules are preferentially recruited to the distal layer of the PSD. Incubation in medium supplemented with zinc (50 µM ZnCl2, 1 hr) also significantly increased labeling intensity for Shank3 at the PSD, but this addition of Shank3 was not preferential to the distal layer. When cells were incubated with zinc and then treated with NMDA, labeling intensity of Shank3 became higher than with either treatment alone and manifested a preference for the distal layer of the PSD. Without zinc supplementation, NMDA-induced accumulation of Shank3 at the PSD was transient, reversing within 30 min after return to control medium. However, when zinc was included in culture media throughout the experiment, the NMDA-induced accumulation of Shank3 was largely retained, including Shank3 molecules recruited to the distal layer of the PSD. These results demonstrate that activity induces accumulation of Shank3 at the PSD and that zinc stabilizes PSD-associated Shank3, possibly through strengthening of Shank-Shank association.

AIDA-1 Moves out of the Postsynaptic Density Core under Excitatory Conditions.

AIDA-1 is highly enriched in postsynaptic density (PSD) fractions and is considered a major component of the PSD complex. In the present study, immunogold electron microscopy was applied to determine localization as well as the activity-induced redistribution of AIDA-1 at the PSD using two antibodies that recognize two different epitopes. In cultured rat hippocampal neurons under basal conditions, immunogold label for AIDA-1 is mostly located within the dense core of the PSD, with a median distance of ~30 nm from the postsynaptic membrane. Under excitatory conditions, such as depolarization with high K+ (90 mM, 2 min) or application of NMDA (50 µM, 2 min), AIDA-1 label density at the PSD core is reduced to 40% of controls and the median distance of label from the postsynaptic membrane increases to ~55 nm. The effect of excitatory conditions on the postsynaptic distribution of AIDA-1 is reversed within 30 minutes after returning to control conditions. The reversible removal of AIDA-1 from the PSD core under excitatory conditions is similar to the redistribution of another abundant PSD protein, SynGAP. Both SynGAP-alpha1 and AIDA-1 are known to bind PSD-95. Activity-induced transient translocation of these abundant proteins from the PSD core could promote structural flexibility, vacate sites on PSD-95 for the insertion of other components and thus may create a window for synaptic modification.

Role of glial cells in axonal regeneration.

Axonal regeneration is critical for functional recovery following neural injury. In addition to intrinsic differences between regenerative responses of axons in peripheral versus central nervous systems, environmental factors such as glial cells and related molecules in the extracellular matrix (ECM) play an important role in axonal regeneration. Schwann cells in the peripheral nervous system (PNS) are recognized as favorable factors that promote axonal regeneration, while astrocytes and oligodendrocytes in the central nervous system (CNS) are not. In this review, we evaluate the roles of Schwann cells and astrocytes in axonal regeneration and examine recent evidence that suggests a dual function of astrocytes in regenerative responses. We also discuss the role of Cdc2 pathways in axonal regeneration, which is commonly activated in Schwann cells and astrocytes. Greater insight on the roles of glial cells in axonal regeneration is key to establishing baseline interventions for improving functional recovery following neural injury.