ABSTRACT
BACKGROUND: Regional anesthesia has been associated with improved postoperative outcomes. Disparities in regional anesthesia utilization exist; however, no studies have examined utilization rates as a function of hospital region. METHODS: A national hospital database (Hospital Corporation of America {HCA}) was queried for patients aged 18 years or older that received selected surgical procedure codes between January 2016 and June 2021. Surgical procedures included were total knee arthroplasty (TKA), total shoulder arthroplasty (TSA), anterior cruciate ligament reconstruction (ACLR), carpal tunnel release, total abdominal hysterectomy (TAH), open reduction and internal fixation (ORIF) of the ankle, and arteriovenous (AV) fistula creation. Regional anesthesia was defined as any form of neuraxial and/or peripheral nerve blocks. Basic summary statistics were utilized to calculate the rates of regional anesthesia (RA), and chi-squared analyses were calculated to determine significant differences in the rate of RA utilization. RESULTS: There were 52,068 patients included in this study, of which 2,114 (4.1%) received RA. The greatest RA rates were for TSA (5.8%), TKA (4.5), and anterior cruciate ligament reconstruction (ACLR) (3.6%), whereas the lowest RA rate was for TAH (1.1%). For the TKA cohort, the Midwest had a significantly greater utilization rate than the South or West (10.9% vs. 4.8% or 3.1%, p<0.001). The Midwest also had the highest utilization rate in the ACLR cohort (8.1%, p<0.001), TAH cohort (16.7%, p<0.001), and AV fistula cohort (6.4%, p<0.001). For the carpal tunnel cohort, the West had the highest utilization rate (11.8% vs. 8.1%, 1.1%, 0%, p<0.001). The West region also had the highest utilization rate for the ankle ORIF (7.8%, p<0.001). No significant differences were found by region for TSA (p=0.31). CONCLUSION: Significant variations in RA utilization rates were found by region, with the West having the highest utilization for ankle ORIF and carpal tunnel, and the Midwest having the highest rate for TKA, ACLR, TAH, and AV fistula.
ABSTRACT
Growth factors and transcription factors are well known to regulate pluripotent stem cells, but less is known about translational control in stem cells. Here, we use embryonic stem cells (ESCs) to investigate a connection between ESC growth factors and eIF2α-mediated translational control (eIF2α phosphorylation promotes protein expression from mRNAs with upstream open-reading frames, or uORFs). We find abundant phosphorylated P-eIF2α (P-eIF2α) in both pluripotent mouse and human ESCs, but little P-eIF2α in ESCs triggered to differentiate. We show that the growth factors LIF (leukemia inhibitory factor) and BMP4 (bone morphogenic protein 4) both maintain P-eIF2α in mESCs, but use distinct mechanisms: LIF inhibits an eIF2α phosphatase whereas BMP4 activates an eIF2α kinase. The mRNAs encoding the pluripotency factors Nanog and c-Myc possess uORFs while Oct4 mRNA does not. We find that salubrinal, a chemical that increases eIF2α phosphorylation, promotes Nanog and c-Myc expression, but not Oct4 expression. These experiments connect ESC growth factors to eIF2α phosphorylation and suggest a chemical substitute for LIF to enhance Nanog and c-Myc expression.
Subject(s)
Bone Morphogenetic Protein 4/pharmacology , Eukaryotic Initiation Factor-2/metabolism , Human Embryonic Stem Cells/metabolism , Leukemia Inhibitory Factor/pharmacology , Mouse Embryonic Stem Cells/metabolism , Animals , Cell Line , Cinnamates/pharmacology , Eukaryotic Initiation Factor-4G/metabolism , Homeodomain Proteins/metabolism , Human Embryonic Stem Cells/drug effects , Humans , Mice , Models, Biological , Mouse Embryonic Stem Cells/drug effects , Nanog Homeobox Protein , Phosphorylation/drug effects , Proto-Oncogene Proteins c-myc/metabolism , Thiourea/analogs & derivatives , Thiourea/pharmacologyABSTRACT
OBJECTIVES: Primary isolated dental follicle stem cells (DFSCs) possess a strong osteogenesis capability, and such capability is reduced during in vitro culture. Because dentin matrix protein 1 (DMP1) is essential in the maturation of osteoblasts, our objectives were to determine (1) the expression of DMP1 in the DFSCs, (2) the correlation between DMP1 expression and osteogenic capability of DFSCs, and (3) the ability of DMP1 to promote osteogenic differentiation of DFSCs. METHODS: DFSCs and their non-stem cell counterpart dental follicle cells (DFC) were established from postnatal rat pups. Expression of DMP1 in the DFSCs and DFC was determined using real-time RT-PCR and western blotting. Different passages of DFSCs were subjected to osteogenic induction. The correlation between osteogenesis and DMP1 expression was analyzed. Then, expression of DMP1 in the DFSCs was knocked-down using siRNA, followed by osteogenic induction to evaluate the effect of DMP1-knockdown. Finally, the late passage DFSCs with reduced DMP1 expression and osteogenic capability were cultured in osteogenic induction medium containing mouse recombinant DMP1 (mrDMP1) to determine if DMP1 can restore osteogenesis of DFSCs. RESULTS: DFSCs expressed much higher levels of DMP1 than did DFC. DMP1 expression was correlated with the osteogenic capability of DFSCs. Knockdown of DMP1 expression markedly decreased the osteogenesis and osteogenic gene expression in the DFSCs whereas adding mrDMP1 protein to the osteogenic induction medium enhanced osteogenesis. CONCLUSIONS: DMP1 is highly expressed in the DFSCs, but minimally expressed in non-stem cell DFC. DMP1 appears to play an important role for osteogenic differentiation of the DFSCs.
