Engineering of Janus-Like Dendrimers with Peptides Derived from Glycoproteins of Herpes Simplex Virus Type 1: Toward a Versatile and Novel Antiviral Platform.

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol-ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.

Intensive Cryotherapy in the Emergency Department (ICED): A Randomized Controlled Trial.

INTRODUCTION: Pain control is an essential component of musculoskeletal injury treatment in the emergency department (ED). We evaluated the most effective type of cryotherapy for analgesia of acute musculoskeletal injury and the impact on opioid utilization. METHODS: This was a prospective, randomized, single-blind controlled trial of adult ED patients who presented with acute musculoskeletal pain. Patients were randomized to either intensive targeted cryotherapy (crushed wetted ice in a plastic bag) or agitated chemical cold pack applied to the injury site for 20 minutes. All other diagnostic and therapeutic orders were at the discretion of the treating physician. Visual analog pain scores were measured at the time of cryotherapy application, at 20 minutes (time of cryotherapy removal), and at 60 minutes (40 minutes after removal). RESULTS: We enrolled 38 patients, 17 randomized to intensive targeted cryotherapy and 21 to chemical cold packs, with well-matched demographics. The intensive targeted cryotherapy group achieved significantly greater pain relief at 20 minutes (2.1 [95% confidence interval (CI), 1.3 - 2.9] vs 0.9 [95% CI, 0.3 - 1.5], P < 0.05) and at 60 minutes (2.7 [95% CI, 1.6 - 3.7] vs 1.2 [95% CI, 0.6 - 1.7], P < 0.05), number need to trial (NNT) = 3.2. Opioid administration in the ED was significantly lower in the intensive targeted cryotherapy group (1 [6%] vs 7 [33%], P < 0.05), NNT = 3.6. Those who received a discharge opiate prescription had significantly higher 60-minute pain scores (7.3 ± 2.2 vs 4.1 ± 2.7, P < 0.05). CONCLUSION: Intensive targeted cryotherapy provided more effective analgesia than chemical cold packs for acute musculoskeletal injuries in the ED and may contribute to lower opioid usage.