Rod derotation techniques for thoracolumbar spinal deformity

Journal ArticleOBJECTIVE: The operative correction of scoliosis requires multiple intraoperative techniques and tools to achieve an adequate result. Frequently, multiple methods are used to accomplish this, such as rod cantilever techniques, in situ bending, Smith-Petersen and pedicle subtraction osteotomies, closed reduction methods, and rod derotation techniques. Rod derotation techniques will be reviewed and discussed in this article. METHODS: A review of the available literature on anterior and posterior rod derotation is performed with a case example of the authors' experience utilizing this technique. RESULTS: Rod derotation is one technique that can transform a pathological scoliotic curve to normal physiological kyphosis or lordosis by simply rotating a rod intraoperatively. CONCLUSION: In this article, the authors present rod derotation as a valuable technique in the surgical arsenal for the treatment of scoliosis, including a discussion of the technique and its limitations

Synthetic peripherally-restricted cannabinoid suppresses chemotherapy-induced peripheral neuropathy pain symptoms by CB1 receptor activation.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe and dose-limiting side effect of cancer treatment that affects millions of cancer survivors throughout the world and current treatment options are extremely limited by their side effects. Cannabinoids are highly effective in suppressing pain symptoms of chemotherapy-induced and other peripheral neuropathies but their widespread use is limited by central nervous system (CNS)-mediated side effects. Here, we tested one compound from a series of recently developed synthetic peripherally restricted cannabinoids (PRCBs) in a rat model of cisplatin-induced peripheral neuropathy. Results show that local or systemic administration of 4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3-yl]ethyl}morpholine (PrNMI) dose-dependently suppressed CIPN mechanical and cold allodynia. Orally administered PrNMI also dose-dependently suppressed CIPN allodynia symptoms in both male and female rats without any CNS side effects. Co-administration with selective cannabinoid receptor subtype blockers revealed that PrNMI's anti-allodynic effects are mediated by CB1 receptor (CB1R) activation. Expression of CB2Rs was reduced in dorsal root ganglia from CIPN rats, whereas expression of CB1Rs and various endocannabinoid synthesizing and metabolizing enzymes was unaffected. Daily PrNMI treatment of CIPN rats for two weeks showed a lack of appreciable tolerance to PrNMI's anti-allodynic effects. In an operant task which reflects cerebral processing of pain, PrNMI also dose-dependently suppressed CIPN pain behaviors. Our results demonstrate that PRCBs exemplified by PrNMI may represent a viable option for the treatment of CIPN pain symptoms

Unified description of fission in fusion and spallation reactions

We present a statistical-model description of fission, in the framework of compound-nucleus decay, which is found to simultaneously reproduce data from both heavy-ion-induced fusion reactions and proton-induced spallation reactions at around 1 GeV. For the spallation reactions, the initial compound-nucleus population is predicted by the Li\`{e}ge Intranuclear Cascade Model. We are able to reproduce experimental fission probabilities and fission-fragment mass distributions in both reactions types with the same parameter sets. However, no unique parameter set was obtained for the fission probability. The introduction of fission transients can be offset by an increase of the ratio of level-density parameters for the saddle-point and ground-state configurations. Changes to the finite-range fission barriers could be offset by a scaling of the Bohr-Wheeler decay width as predicted by Kramers. The parameter sets presented allow accurate prediction of fission probabilities for excitation energies up to 300 MeV and spins up to 60 \hbar.Comment: 16 pages, 20 figures. Submitted to Phys. Rev.

Hydrologic and Hydraulic Modeling of the Tunnel and Reservoir Plan System in Northeastern Illinois

The Tunnel and Reservoir Plan (TARP) was adopted by the Metropolitan Sanitary District of Greater Chicago in 1972 to address combined sewer overflow (CSO) pollution and flooding problems in 970 km2 of the Chicago metropolitan area served by combined sewers. TARP consists of about 175 km of tunnels, three reservoirs, 256 drop shafts, and over 600 connecting structures, pumping stations, and other appurtenances for the capture and storage of CSOs and for conveying the stored CSOs to water reclamation plants for treatment. The TARP system is comprised of three independent systems: the Calumet system serving the south suburbs and a portion of the south side of Chicago, the Upper Des Plaines system serving the northwest suburbs, and the Mainstream/ Des Plaines system serving the remainder of Chicago and the north, west and southwest suburbs. The Metropolitan Water Reclamation District of Greater Chicago (MWRDGC) desires to develop new, updated and enhanced computer models to allow for simulation of the TARP systems. The new models will be used to optimize operation of the system as actually constructed, to determine constraints in the system, identify physical changes that may be needed to improve performance, and allow what-if analyses to be performed for potential storm scenarios and facility revisions. The modeling includes development of a Physical Inventory system, Hydraulic Modeling of the TARP systems, and Hydrologic Modeling of the TARP service areas. The Physical Inventory provides a digital description of the physical geometry of the TARP system and the related hydraulic performance of system components. Hydrologic Modeling uses data for each dropshafts service area to determine hydrographs describing the inflows to the TARP systems. A ma jor component of the Hydrologic Modeling is to develop tools and methods that allow robust simulation of the extreme heterogeneity of highly urbanized systems and that provide guidance for data compilation needed to improve the accuracy of such simulations. Hydraulic Modeling uses the information from the Physical Inventory and the Hydrologic Modeling to simulate hydraulic response of the TARP system to different inputs. The Hydraulic Modeling tools developed are capable of simulating the range of possible flows in the system, from gravity flows over a dry bed to mixed gravity/surcharged flows to shocks and hydraulic transients

Nitrosylcobalamin Potentiates the Anti-Neoplastic Effects of Chemotherapeutic Agents via Suppression of Survival Signaling

Nitrosylcobalamin (NO-Cbl) is a chemotherapeutic pro-drug derived from vitamin B12 that preferentially delivers nitric oxide (NO) to tumor cells, based upon increased receptor expression. NO-Cbl induces Apo2L/TRAIL-mediated apoptosis and inhibits survival signaling in a variety of malignant cell lines. Chemotherapeutic agents often simultaneously induce an apoptotic signal and activation of NF-kappaB, which has the undesired effect of promoting cell survival. The specific aims of this study were to 1) measure the anti-tumor effects of NO-Cbl alone and in combination with conventional chemotherapeutic agents, and to 2) examine the mechanism of action of NO-Cbl as a single agent and in combination therapy.Using anti-proliferative assays, electrophoretic mobility shift assay (EMSA), immunoblot analysis and kinase assays, we demonstrate an increase in the effectiveness of chemotherapeutic agents in combination with NO-Cbl as a result of suppressed NF-kappaB activation.Eighteen chemotherapeutic agents were tested in combination with NO-Cbl, in thirteen malignant cell lines, resulting in a synergistic anti-proliferative effect in 78% of the combinations tested. NO-Cbl pre-treatment resulted in decreased NF-kappaB DNA binding activity, inhibition of IkappaB kinase (IKK) enzymatic activity, decreased AKT activation, increased caspase-8 and PARP cleavage, and decreased cellular XIAP protein levels.The use of NO-Cbl to inhibit survival signaling may enhance drug efficacy by preventing concomitant activation of NF-kappaB or AKT

Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases

Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non‐native polyketide substrates. Reactions pairing wildtype PKS modules with non‐native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non‐cognate TE domains was severely reduced. In contrast, non‐native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wild‐type polyketide synthases with non‐native substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of non‐native substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/3/anie202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/2/anie202004991_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156208/1/anie202004991.pd

Probing Selectivity and Creating Structural Diversity Through Hybrid Polyketide Synthases

Engineering polyketide synthases (PKS) to produce new metabolites requires an understanding of catalytic points of failure during substrate processing. Growing evidence indicates the thioesterase (TE) domain as a significant bottleneck within engineered PKS systems. We created a series of hybrid PKS modules bearing exchanged TE domains from heterologous pathways and challenged them with both native and non‐native polyketide substrates. Reactions pairing wildtype PKS modules with non‐native substrates primarily resulted in poor conversions to anticipated macrolactones. Likewise, product formation with native substrates and hybrid PKS modules bearing non‐cognate TE domains was severely reduced. In contrast, non‐native substrates were converted by most hybrid modules containing a substrate compatible TE, directly implicating this domain as the major catalytic gatekeeper and highlighting its value as a target for protein engineering to improve analog production in PKS pathways.Improved catalysis with engineered polyketide synthases: Pairing wild‐type polyketide synthases with non‐native substrates largely failed to produce the anticipated products. A series of hybrid modules bearing heterologous thioesterase domains were generated and employed to alleviate the observed catalytic bottleneck, resulting in the efficient processing of non‐native substrates and an unexpected path to product diversity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/2/ange202004991-sup-0001-misc_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/1/ange202004991.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156161/3/ange202004991_am.pd