While the Mre11-Rad50-Nbs1 (MRN) complex has known roles in repair processes like homologous recombination and microhomology-mediated end-joining, its role in nonhomologous end-joining (NHEJ) is unclear as ,, and mammals have different requirements for repairing cut DNA ends. Most double-strand breaks (DSBs) require nucleolytic processing prior to DNA ligation. Therefore, we studied repair using the transposon, whose excision leaves a DSB capped by hairpin ends similar to structures generated by palindromes and trinucleotide repeats. We generated single insertions using a novel transient transfection system, and used excision to show a requirement for MRN in the NHEJ of nonligatable ends. NHEJ repair was indicated by the >1000-fold decrease in excision in cells lacking Ku or DNA ligase 4. Most repaired excision sites had <5 bp of sequence loss or mutation, characteristic for NHEJ and similar excision events in metazoans, and in contrast to the more extensive loss seen in NHEJ was reduced>1000-fold in cells lacking each MRN subunit, and loss of MRN-associated Ctp1 caused a 30-fold reduction. An Mre11 dimer is thought to hold DNA ends together for repair, and Mre11 dimerization domain mutations reduced repair 300-fold. In contrast, a mutant defective in endonucleolytic activity, the same mutant lacking Ctp1, or the triple mutant also lacking the putative hairpin nuclease Pso2 showed wild-type levels of repair. Thus, MRN may act to recruit the hairpin opening activity that allows subsequent repair.
Thyrotoxic hypokalemic periodic paralysis (THPP) is a condition that results in transient skeletal muscle paralysis secondary to intracellular potassium sequestration. Susceptible individuals often have an underlying channelopathy, which may be exacerbated by lifestyle factors or underlying medical comorbidities such as hyperthyroidism or diarrheal illness. Classically, THPP presents with paralysis of proximal extremity musculature. In this case, we present a rare case of unilateral THPP. Such a presentation is relevant to emergency physicians as it mimics a stroke or transient ischemic attack and should be considered on the differential for unilateral neurologic deficits.
Auricular hematoma drainage is a crucial skill that emergency medicine providers must be proficient in to prevent complications including permanent deformity of the ear. We aimed to develop and evaluate a costeffective task trainer to allow emergency medicine (EM) residents to practice the key skills of auricular hematoma drainage and pressure dressing application.After creating a task trainer out of a bell pepper, we implemented this training during our EM simulation conference with a total of 20 PGY 1-3 EM residents. Prior to the simulation session, a survey of all 39 residents found a rated confidence level of auricular hematoma drainage as low on a five-point Likert scale (mean: 2.2 (standard deviation (SD): 1.08)). After the session, the 20 EM residents who participated were much more confident in their ability to perform this procedure (mean: 4.4 (SD: 0.6)). This low-cost, easy-to-create auricular hematoma drainage and repair task trainer was well received by our EM residents and led to an improved resident comfort level in performing this necessary EM procedure. This task trainer can be used by EM trainees of all levels as a tool to increase their skill and comfort level when performing the crucial procedure of auricular hematoma drainage and repair.
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