Cyclic stretch has been shown to alter cell physiology, cytoskeletal structure, signal transduction, and gene expression in a variety of cell types. To determine the effects of stretch on the gene ...transfer process, we compared the transfection efficiencies of human A549 cells grown either statically or exposed to 10% cyclic stretch (Δ surface area) at 60 cycles/min (1 Hz) for 24 hours prior to, and/or after transfection with pEGFP-N1 and pCMV-lux-DTS using lipoplex or electroporation. Stretching the cells prior to transfection had no effect on gene transfer. By contrast, cyclic, but not continuous, stretch applied immediately after transfection for as little as 30 minutes resulted in a 10-fold increase in gene transfer and expression by either transfection technique. These stretch conditions did not result in rupture of the plasma membrane based on the fact that DNA was unable to enter stretched cells unless either an electric field was applied or the DNA was complexed with liposomes. Taken together with the timing of the stretch response and the known effects of stretch on transcription, these findings suggest that cyclic stretch may be altering the intracellular transport of plasmids to increase gene expression.
Cervical disc arthroplasty (CDA) has emerged as an alternative surgical option to anterior cervical discectomy and fusion (ACDF) for cervical disc pathology, with recent trials demonstrating ...non-inferiority of CDA to ACDF. While short-term trends regarding utilization rates, revision procedures and complications have been explored, longer-term outcomes, specifically involving re-operation rates and type of reoperation are lacking. Therefore, we used the New York Statewide Planning and Research Cooperative Systems (SPARCS) database to characterize subsequent cervical spine surgery in patients undergoing primary elective CDA and ACDF.
Characterize subsequent cervical spine surgery in patients undergoing primary elective CDA and ACDF.
Retrospective state database study.
Patients who underwent elective inpatient CDA and ACDF in New York State.
We analyzed the SPARCS inpatient database from 2005 to 2013 to identify patients who underwent elective inpatient CDA and ACDF procedures. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to extract the index procedures (CDA: 84.61, 84.62; ACDF: 81.02) and to identify patient demographics and cervical re-operation procedures. Patients were longitudinally followed until September 2015, corresponding to a minimum of two year follow-up, to determine the incidence of subsequent cervical spine reoperation, which included another primary CDA or ACDF, revision CDA or ACDF, and posterior cervical fusion. Logistic regression analysis was used to determine the odds of subsequent cervical spine reoperation.
Between January 2005 and September 2013, 731 patients underwent an inpatient CDA and 45,204 underwent an inpatient ACDF. Patients undergoing CDA were more likely to be younger (43.6 vs. 50.7, p<.0001), to have fewer comorbidities (p<.001), and to have a cervical diagnosis of disc displacement (68.4% vs. 46.5%, p<.001). Subsequent cervical spine reoperation rates did not differ at one (OR=1.06, 95%CI=0.60–1.89, p=.840) or two years (OR=1.35, 95%CI=0.95–1.94, p=.099) postoperatively. When analyzing subsequent cervical reoperations, CDA patients were 29 times more likely to return to the operating room to receive a primary ACDF procedure compared to ACDF patients returning to undergo a primary CDA procedure (OR=29.13, 95%CI: 19.52–43.48, p<.001). Patients undergoing CDA had a decreased odds of undergoing another CDA primary procedure at adjacent cervical levels compared to ACDF patients undergoing another primary cervical ACDF procedure (OR:0.17, 95%CI:0.07–0.46, p<.001). Patients undergoing CDA had a decreased odds of undergoing revision CDA compared to ACDF patients undergoing revision ACDF (OR:0.41, 95%CI:0.17–0.98, p=.045). The most common reason for subsequent cervical re-operation after CDA or ACDF was cervical disc displacement (CDA: 28.6%, ACDF: 21.4%).
Compared to patients undergoing ACDF, patients undergoing CDA are more likely to be younger, to have fewer comorbidities and to have a primary diagnosis of cervical disc displacement. While there is no significant difference in subsequent cervical spine re-operation rates between ACDF and CDA, surgeons performing revision procedures at the same cervical level or performing primary procedures at adjacent cervical levels are more likely to utilize ACDF rather than CDA. Further investigation in outpatient primary and revision cervical spine cases is needed to assess these findings.
This abstract does not discuss or include any applicable devices or drugs.
In recent years, cervical disc arthroplasty (CDA) has emerged as an alternative surgical option to cervical arthrodesis. CDA is a motion-sparing device that mimics natural cervical motion, ...theoretically reducing adjacent level pathology. Surgical intervention rates following CDA have been reported via the FDA IDE studies as well as in several larger series. However, these studies and their findings may not be generalizable to the spine surgery community.
Identify risk factors and incidence of subsequent cervical spine surgery in patients undergoing primary CDA.
New York Statewide Planning and Research Cooperative Systems (SPARCS) database.
We analyzed the SPARCS inpatient database from 2005 to 2015 to identify patients who underwent isolated CDA. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to extract the index CDA procedure (84.61, 84.62) and to identify patient demographics and re-operation procedures. Patients were longitudinally followed until September 2015, corresponding to a minimum of two-year follow-up, to determine the incidence of subsequent cervical spine re-operation, which included another primary CDA, revision CDA, anterior cervical discectomy and fusion (ACDF), posterior cervical fusion (PCF), and laminectomy without fusion. Univariate and multivariate analyses were used to identify demographic risk factors for subsequent re-operation.
A total of 835 patients underwent an inpatient CDA procedure between January 2005 and September 2013. After 2007, there was a decreasing number of inpatient CDA procedures performed in New York State (m=−33 cases/year, p
We identified a 7.5% incidence of subsequent cervical spine surgery after inpatient CDA, and a 4.4% re-operation rate at two years. Inpatient CDA procedures have been declining since 2008. Female sex was the only patient demographic factor to significantly influence the odds of cervical spine re-operation. Further investigation is needed to evaluate for the presence of these trends in outpatient databases.
This abstract does not discuss or include any applicable devices or drugs.
In the United States, the federal government and several state governments are formulating or implementing policies aimed at reducing greenhouse gases emissions. In April 2009, the State of ...California adopted the Low-Carbon Fuel Standard (LCFS), a groundbreaking policy for reducing greenhouse gas emissions in the transportation sector. This paper reviews the major elements of a LCFS, focusing on California's implementation, and discusses the key open issues of a LCFS. This paper also summarizes the major elements of the cap-and-trade and carbon tax concepts, the two principal alternative approaches to regulating greenhouse gases emissions. Analytical issues associated with the LCFS are highlighted, including land-use change effects associated with certain biofuels. If electricity becomes a significant transportation fuel, a number of regulatory issues will need to be addressed. Beyond California, the LCFS approach appears to be favored by several other US states and the European Union. A Hydrogen-Success scenario example illustrates the key features of a national LCFS following California's model.
Selective inhibitors of sodium glucose cotransporter-2 (SGLT2) are widely used for the treatment of type 2 diabetes and act primarily to lower blood glucose by preventing glucose reabsorption in the ...kidney. However, it is controversial whether these agents also act on the pancreatic islet, specifically the alpha cell, to increase glucagon secretion. To determine the effects of SGLT2 on human islets, we analyzed SGLT2 expression and hormone secretion by human islets treated with the SGLT2 inhibitor dapagliflozin (DAPA) in vitro and in vivo. Compared to the human kidney, SLC5A2 transcript expression was 1600-fold lower in human islets and SGLT2 protein was not detected. In vitro, DAPA treatment had no effect on glucagon or insulin secretion by human islets at either high or low glucose concentrations. In mice bearing transplanted human islets, 1 and 4 weeks of DAPA treatment did not alter fasting blood glucose, human insulin, and total glucagon levels. Upon glucose stimulation, DAPA treatment led to lower blood glucose levels and proportionally lower human insulin levels, irrespective of treatment duration. In contrast, after glucose stimulation, total glucagon was increased after 1 week of DAPA treatment but normalized after 4 weeks of treatment. Furthermore, the human islet grafts showed no effects of DAPA treatment on hormone content, endocrine cell proliferation or apoptosis, or amyloid deposition. These data indicate that DAPA does not directly affect the human pancreatic islet, but rather suggest an indirect effect where lower blood glucose leads to reduced insulin secretion and a transient increase in glucagon secretion. (Endocrinology 161: 1-12, 2020) Key Words: diabetes, islet, insulin, glucagon
Nuclear import of plasmid DNA in nondividing cells is a process essential to the success of numerous viral life cycles, gene therapy protocols, and gene expression experiments. Here, intact ...protein-free SV40 DNA was cytoplasmically injected into cells and its subcellular localization was followed by
in situhybridization. SV40 DNA localized to the nucleus consistent with a mechanism of transport through the nuclear pore complex (NPC): import was inhibited by the addition of the NPC-inhibitory agents wheat germ agglutinin and an anti-nucleoporin antibody as well as by energy depletion. DNA transport appeared to be a multistep process with the DNA accumulating at the nuclear periphery before its import. Most importantly, nuclear import was sequence specific: a region of SV40 DNA containing the origin of replication and the early and late promoters supported import, whereas bacterial sequences alone and other SV40-derived sequences did not. The majority of the imported DNA colocalized with the SC-35 splicing complex antigen, suggesting that the intranuclear DNA localizes to areas of transcription or message processing. This link to transcription was strengthened by the finding that inhibition of transcription blocked DNA import but not protein nuclear import. Taken together, these results support a model in which plasmid DNA nuclear import occurs by a mechanism similar to that used by nuclear localization signal-containing proteins but is also dependent on transcription.
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