The therapeutic potential of small interfering RNAs (siRNAs) is severely limited by the availability of delivery platforms that protect siRNA from degradation, deliver it to the target cell with high specificity and efficiency, and promote its endosomal escape and cytosolic dispersion. Here we report that mesoporous silica nanoparticle-supported lipid bilayers (or ‘protocells’), exhibit multiple properties that overcome many of the limitations of existing delivery platforms. Protocells have a 10- to 100-fold greater capacity for siRNA than corresponding lipid nanoparticles and are markedly more stable when incubated under physiological conditions. Protocells loaded with a cocktail of siRNAs bind to cells in a manner dependent on the presence of an appropriate targeting peptide and, through an endocytic pathway followed by endosomal disruption, promote delivery of the silencing nucleotides to the cytoplasm. The expression of each of the genes targeted by the siRNAs was shown to be repressed at the protein level, resulting in a potent induction of growth arrest and apoptosis. Incubation of control cells that lack expression of the antigen recognized by the targeting peptide with siRNA-loaded protocells induced neither repression of protein expression nor apoptosis, indicating the precise specificity of cytotoxic activity. In terms of loading capacity, targeting capabilities, and potency of action, protocells provide unique attributes as a delivery platform for therapeutic oligonucleotides.

Mesoporous silica nanoparticle‐supported lipid bilayers, or “protocells”, exhibit a high loading capacity, enhanced colloidal stability, and peptide‐directed, cell‐specific uptake, making them especially well‐suited for targeted delivery of protein toxins to cancer. Protocells loaded with ricin toxin A‐chain (RTA) and targeted to hepatocellular carcinoma cause complete cell death at 30 pM of RTA without affecting the viability of control hepatocytes.

BackgroundMisclassification of wounds in the operating room (OR) can adversely affect surgical site infection (SSI) reporting and reimbursement. This study aimed to measure the effects of a curriculum on documentation of surgical wound classification (SWC) for operating room staff and surgeons.MethodsAccuracy of SWC was determined by comparing SWC documented by OR staff during the original operation to SWC determined by in-depth chart review. Patients 18 years or older undergoing inpatient surgical procedures were included. Two plan-do-act-study (PDSA) cycles were implemented over the course of 9 months. A total of 747 charts were reviewed. Accuracy of SWC documentation was retrospectively assessed across 248 randomly selected surgeries during a 5-week period prior to interventions and compared to 244 cases and 255 cases of post-intervention data from PDSA1 and PDSA2, respectively. Changes in SWC accuracy were assessed pre- and post-intervention using the kappa coefficient. A p-value for change in agreement was computed by comparing pre- and post-intervention kappa.ResultsInaccurate documentation of surgical wound class decreased significantly following curriculum implementation (kappa improved from 0.553 to 0.739 and 0.757; p = 0.001). Classification accuracy improved across all wound classes; however, class III and IV wounds were more frequently misclassified than class I and II wounds, both before and after the intervention.ConclusionImplementation of a multidisciplinary documentation curriculum resulted in a significant decrease in SWC documentation error. Improved accuracy of SWC reporting may facilitate a better assessment of SSI risk in a complex patient population.

Pica may be related to deficient iron stores in the absence of anemia and can result in serious morbidity. Parenteral iron may be associated with rapid pica resolution in symptomatic pregnant patients.