Improved Metabolic Stability and Silencing Efficacy of siRNAs with Phosphorothioate Linkage-Free, GalNAc-Conjugated Sense Strands Containing Morpholino-LNA Modifications.

To ensure specificity, loading of the sense strand of small interfering RNAs (siRNAs) into RISC must be inhibited. We show here that siRNAs with 5'- and 6'-morpholino LNA residues or 6'-OH-LNA at the 5' terminus of a fully phosphodiester sense strand resulted in metabolically stable siRNAs with a potency and a duration of action in mice that were greater than those of an siRNA in which the 5' terminus of the sense strand has two terminal phosphorothioate linkages and regular LNA.

The Impact of Early Exposure to Microsurgery Training on Undergraduates: A Pilot Course.

Introduction: This case study aimed to investigate a disparity in the medical education pipeline by investigating the impact of fundamental microsurgical training on interest and desire to pursue a career in medicine. This research introduces a method to attract undergraduate students from various backgrounds to the field of microsurgery through a hands-on microsurgical training course.

Methods: Microsurgical training took place 6 hours a week for 6 weeks.

Resuscitation strategies for surgical patients in the neonatal intensive care unit.

Resuscitation of an infant with surgical complications includes both perioperative and post-operative management. In most cases this requires a multidisciplinary approach to achieve the best outcomes. Challenges include immediate expert management at infant delivery with the use of protocolized care, available anesthesia expertise, close monitoring of electrolytes with prompt attention to fluid status, and meticulous pain management.

Open Reduction in Traumatic Cervical Facet Dislocation Does Not Delay Time to Treatment.

Background Cervical facet dislocation is a serious injury that can result in permanent neurologic damage. Current guidelines recommend immediate closed reduction of cervical dislocations, though the efficacy of this practice remains a debate. This study aims to evaluate whether immediate open reduction and fixation of cervical dislocations offer equal or better outcomes for patients and limit the need for follow-up operations.

Single-Stranded Hairpin Loop RNAs (loopmeRNAs) Potently Induce Gene Silencing through the RNA Interference Pathway.

Synthetic small interfering RNAs conjugated to trivalent -acetylgalactosamine (GalNAc) are clinically validated drugs for treatment of liver diseases. Incorporation of phosphorothioate linkages and ribose modifications are necessary for stability, potency, and duration of pharmacology. Although multiple alternative siRNA designs such as Dicer-substrate RNA, shRNA, and circular RNA have been evaluated in vitro and in preclinical studies with some success, clinical applications of these designs are limited as it is difficult to incorporate chemical modifications in these designs.