Experience in Providing Ambulatory Surgery From an Expeditionary Fast Transport Mobile and Rapidly Deployable Expeditionary Medical Unit During Continuing Promise 2018.

INTRODUCTION: This article describes the surgical component of the Continuing Promise 2018 (CP-18) medical training and military cooperation mission. We report on the surgical experience and lessons learned from performing peacetime ambulatory surgeries in a tent-based facility constructed on partner nation territory. METHODS: This CP mission was unique in utilizing a land-based expeditionary surgical facility. Institutional Review Board approval was obtained to collect prospective deidentified patient data and aggregate information on all surgical cases performed. Specific aims of this study included describing surgical patient characteristics and evaluating conservatively selected cases performed in this environment. Body mass index (BMI) was used as a crude screening tool for perioperative risk to assist patient selection. Our secondary aim was to report lessons learned from preparation, logistics, and host nation exchanges. The team coordinated medical credentialing and documentation of all medical supplies with each host nation. Advance teams collaborated with local physicians in country to arrange training exchanges and identify surgical candidates. RESULTS: The mission was conducted from February to April 2018. Only two of five planned partner nation visits were completed. The surgical facility supported 78 procedures over 14 surgical days, averaging over six cases performed per core surgical day. Patients were predominantly female, with a mean age of 25.4 and a mean BMI of 31.1. The average surgical time was 37.5 minutes, the average anesthesia time was 70 minutes, and the average recovery time was 47.6 minutes. No significant complications or adverse events were noted. CONCLUSIONS: CP-18 was the first CP mission to perform elective ambulatory surgery on foreign soil using a tent-based facility in a noncombat, nondisaster environment instead of a hospital or amphibious ship. This mission demonstrated that such a facility may be employed to safely perform low-risk ambulatory surgeries on carefully selected patients. The Expeditionary Medical Unit, coupled with the fast transport vessel enabled rapid expeditionary surgical facility setup with significant military and disaster relief applications. Expansion of surgical indications should be performed carefully and deliberately to avoid complications and damage to international relationships.

Residual Weakness and Recurarization After Sugammadex Administration in Pediatric Patients: A Case Series.

While shown to be safe for administration in pediatric patients, sugammadex has recently been associated with residual weakness or recurarization. We describe 4 additional cases of pediatric patients with residual or recurrent weakness following rocuronium reversal with sugammadex. Two infant patients developed postoperative ventilatory distress, which was possibly related to recurarization after sugammadex reversal. A third patient received sugammadex with apparent waning of clinical effect and subsequently required neostigmine reversal. A fourth patient was observed to have residual weakness, which led to prolonged intubation despite appropriate train-of-four results after reversal with sugammadex.

Diverse roles for histone H2A modifications in DNA damage response pathways in yeast.

There are many types of DNA damage that are repaired by a multiplicity of different repair pathways. All damage and repair occur in the context of chromatin, and histone modifications are involved in many repair processes. We have analyzed the roles of H2A and its modifications in repair by mutagenizing modifiable residues in the N- and C-terminal tails of yeast H2A and by testing strains containing these mutations in multiple DNA repair assays. We show that residues in both tails are important for homologous recombination and nonhomologous end-joining pathways of double-strand break repair, as well as for survival of UV irradiation and oxidative damage. We show that H2A serine 122 is important for repair and/or survival in each of these assays. We also observe a complex pattern of H2A phosphorylation at residues S122, T126, and S129 in response to different damage conditions. We find that overlapping but nonidentical groups of H2A residues in both tails are involved in different pathways of repair. These data suggest the presence of a set of H2A "damage codes" in which distinct patterns of modifications on both tails of H2A may be used to identify specific types of damage or to promote specific repair pathways.

Histone H2A and Spt10 cooperate to regulate induction and autoregulation of the CUP1 metallothionein.

Copper is an essential cellular cofactor that becomes toxic at high levels. Copper homeostasis is tightly regulated by opposing mechanisms that control copper import, export, and copper binding capacity within the cell. High levels of copper induce the expression of metallothioneins, small sulfhydryl-rich proteins with high metal binding capabilities that serve as neutralizers of toxic levels of metals. In yeast, the CUP1 gene encodes a copper metallothionein that is strongly induced in response to metals and other stress and is subsequently rapidly down-regulated. Activation of CUP1 is mediated by the copper-responsive transcriptional activator AceI, and also requires the histone acetylase Spt10 for full induction. We have examined the role of histone H2A in the normal regulation of the CUP1 gene. We have shown that specific H2A mutations in combination with spt10 deletions result in aberrant regulation of CUP1 expression. Certain lysine mutations in H2A alleviate the transcriptional defect in spt10 Delta strains, though CUP1 activation is still delayed in these mutants; however, CUP1 shutdown is normal. In contrast, serine mutations in H2A prevent CUP1 shutdown when combined with spt10 deletions. In addition, swi/snf mutants exhibit both impaired CUP1 induction and failure to shut down CUP1 normally. Finally, different Spt10-dependent histone acetylation events correlate with induction and shutdown. Taken together, these data indicate that CUP1 transcriptional shutdown, like induction, is an active process controlled by the chromatin structure of the gene. These results provide new insights for the role of chromatin structure in metal homeostasis.

Histone modifications and DNA double-strand break repair.

The roles of different histone modifications have been explored extensively in a number of nuclear processes, particularly in transcriptional regulation. Only recently has the role of histone modification in signaling or facilitating DNA repair begun to be elucidated. DNA broken along both strands in the same region, a double-strand break, is damaged in the most severe way possible and can be the most difficult type of damage to repair accurately. To successfully repair the double-strand break, the cell must gain access to the damaged ends of the DNA and recruit repair factors, and in the case of homologous recombination repair, the cell must also find, colocalize, and gain access to a suitable homologous sequence. In the repair of a double-strand break, the cell must also choose between homologous and non-homologous pathways of repair. Here, we will briefly review the mechanisms of double-strand-break repair, and discuss the known roles of histone modifications in signaling and repairing double-strand breaks.