BackgroundKetamine has been well studied for its efficacy as an analgesic agent. However, intranasal (IN) administration of ketamine has only recently been studied in the emergency setting. The objective of this study was to elucidate the efficacy and adverse effects of a sub-dissociative dose of IN Ketamine compared to IV and IM morphine.MethodsA single-center, randomized, prospective, parallel clinical trial of efficacy and safety of IN ketamine compared to IV and IM morphine for analgesia in the emergency department (ED). A convenience sample of 90 patients aged 18–70 experiencing moderate-severe acute traumatic pain (≥80 mm on 100 mm Visual Analog Scale [VAS]) were randomized to receive either 1.0 mg/kg IN ketamine, 0.1 mg/kg IV MO or 0.15 mg/kg IM MO. Pain relief and adverse effects were recorded for 1 h post-administration. The primary outcome was efficacy of IN ketamine compared to IV and IM MO, measured by “time-to-onset” (defined as a ≥15 mm pain decrease on VAS), as well as time to and degree of maximal pain reduction.ResultsThe 3 study groups showed a highly significant, similar maximal pain reduction of 56 ± 26 mm for IN Ketamine, and 59 ± 22 and 48 ± 30 for IV MO and IM MO, respectively. IN Ketamine provided clinically-comparable results to those of IV MO with regards to time to onset (14.3 ± 11.2 v. 8.9 ± 5.6 min, respectively) as well as in time to maximal pain reduction (40.4 ± 16.3) versus (33.4 ± 18), respectively.ConclusionsIN ketamine shows efficacy and safety comparable to IV and IM MO. Given the benefits of this mode of analgesia in emergencies, it should be further studied for potential clinical applications.Trial registrationRetrospectively registered on 27 June 2016. ClinicalTrials.gov ID: NCT02817477 Electronic supplementary materialThe online version of this article (doi:10.1186/s12873-016-0107-0) contains supplementary material, which is available to authorized users.

Heterochromatin is a common DNA packaging form employed by eukaryotes to constitutively silence transposable elements. Determining which sequences to package as heterochromatin is vital for an organism. Here, we use Drosophila melanogaster to study heterochromatin formation, exploiting position-effect variegation, a process whereby a transgene is silenced stochastically if inserted in proximity to heterochromatin, leading to a variegating phenotype. Previous studies identified the transposable element 1360 as a target for heterochromatin formation. We use transgene reporters with either one or four copies of 1360 to determine if increasing local repeat density can alter the fraction of the genome supporting heterochromatin formation. We find that including 1360 in the reporter increases the frequency with which variegating phenotypes are observed. This increase is due to a greater recovery of insertions at the telomereassociated sequences (50% of variegating inserts). In contrast to variegating insertions elsewhere, the phenotype of telomere-associated sequence insertions is largely independent of the presence of 1360 in the reporter. We find that variegating and fully expressed transgenes are located in different types of chromatin and that variegating reporters in the telomere-associated sequences differ from those in pericentric heterochromatin. Indeed, chromatin marks at the transgene insertion site can be used to predict the eye phenotype. Our analysis reveals that increasing the local repeat density (via the transgene reporter) does not enlarge the fraction of the genome supporting heterochromatin formation. Rather, additional copies of 1360 appear to target the reporter to the telomere-associated sequences with greater efficiency, thus leading to an increased recovery of variegating insertions. KEYWORDS heterochromatin; transposable elements; position-effect variegation; chromatin; Drosophila I N vivo regulation of gene expression occurs in the context of chromatin, the complex structure formed by DNA, histones, and a variety of associated proteins. Two basic types of chromatin were originally distinguished, euchromatin and heterochromatin, based on cytological staining behavior during the cell cycle (Heitz 1928). Euchromatin and heterochromatin differ in a number of characteristics, including biochemical makeup and their effect on the expression of transgene reporters. Euchromatin is generally accessible for transcription, contains the majority of the genes, and is characterized by biochemical marks associated with transcription, such as high levels of histone acetylation, transcriptional activators, and RNA polymerase II. In contrast, heterochromatin contains few genes and has a high repeat density. Heterochromatin is characterized by low levels of histone acetylation, high levels of histone 3 lysine 9 (H3K9) methylation, and the presence of "silencing" proteins such as heterochromatin protein 1 (HP1) (Beisel and Paro 2011). While this model of two basic chromatin types has been very successful...

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A 50-year-old male with past medical history of diabetes mellitus presented with extensive Fournier’s Gangrene. He had a wide-spread area of involvement and the wound vacuum placement involved the entirety of the phallus. We describe a surgical technique where the penis can be diverted from the site of the wound to allow for more secure wound vacuum placement and future reconstructive options.