Bicistronic retroviral vectors were constructed containing the foot-and-mouth disease virus (FMDV) internal ribosome entry site (IRES) followed by the coding region of beta-galactosidase (beta-gal) or therapeutic genes, with the selectable neomycin phosphotransferase gene under the control of the viral long terminal repeat (LTR) promoter. LNFX, a vector with a multiple cloning site 3' to foot-and-mouth disease virus IRES, was used to construct vectors encoding rat erythropoietin (EP), rat granulocyte colony-stimulating factor (G-CSF), human adenosine deaminase (ADA) and beta-gal. In transduced primary rat vascular smooth muscle cells the cytokines were expressed at high levels, similar to those obtained from vectors employing the viral LTR promoter. LNFZ, a vector encoding beta-gal, had a 10-fold increase in titer over that of LNPoZ, a comparable vector containing the poliovirus (Po) internal ribosome entry site. Primary canine vascular smooth muscle cells infected with LNFZ and LNPoZ expressed similar activities of beta-gal and neomycin phosphotransferase (NPT). Overall, these vectors had titers between 10(6) and 2 x 10(7) c.f.u./ml, indicating that foot-and-mouth disease virus IRES provides high-titer bicistronic vectors with high-level two gene expression.
Background: Guidelines offer varying recommendations for preoperative long-acting basal insulin dosing, despite mounting evidence of the advantages of maintaining perioperative glucose levels between 80 and 180 mg/dL. Observations: We iteratively adjusted health care practitioner (HCP) instructions to intensify insulin dosing on the evening before surgery for 195 consecutive patients with diabetes mellitus treated with long-acting basal insulin with an evening dosage. Baseline data was collected in phase 1. In phase 2, the preoperative insulin dose on the evening before surgery was increased for patients with hemoglobin A 1c (HbA 1c ) > 8%; in phase 3, it was increased for patients with HbA 1c ≤ 8% while sustaining the phase 2 change. Increased preoperative insulin doses did not change the rates of day of surgery (DOS) hyperglycemia or hypoglycemia. Overall, HCP adherence to the modified protocols was high (89%). A decline in HCP adherence after phase 2 protocol change was associated with a transient increase in DOS hyperglycemia. Patient adherence to preoperative medication instructions was high (86%) and was not affected by protocol changes. Conclusions: Preoperative insulin intensification the evening before surgery did not change rates of DOS hyperglycemia or hypoglycemia. HCP adherence decreased transiently, which briefly increased DOS hyperglycemia rates in some patients.
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