Return to Work (RTW) programmes have become imperative in manpower scarce countries. This paper describes a RTW programme in a Singapore tertiary hospital, reports patient outcomes and discusses the ...practicality and effectiveness of the programme. Seventy-three workers participated in the programme over a two-year period. A statistically significant increase in work ability and self-perceived overall health status from first contact with worker (baseline) to discharge was observed. Continued programme participation till first RTW was associated with higher work ability and self-perceived overall health status at baseline. The RTW Coordinator-anchored multidisciplinary model which provided holistic support to the worker and addressed stakeholder interests were central to the programme’s success. Greater awareness of RTW programme benefits will improve sustained participation. Our RTW programme features, implementation experiences and participant reported effectiveness may inform the development of improved return to work models.
FokI Dimerization is Required for DNA Cleavage Bitinaite, Jurate; Wah, David A.; Aggarwal, Aneel K. ...
Proceedings of the National Academy of Sciences - PNAS,
09/1998, Letnik:
95, Številka:
18
Journal Article
Recenzirano
Odprti dostop
FokI is a type IIs restriction endonuclease comprised of a DNA recognition domain and a catalytic domain. The structural similarity of the FokI catalytic domain to the type II restriction ...endonuclease BamHI monomer suggested that the FokI catalytic domains may dimerize. In addition, the FokI structure, presented in an accompanying paper in this issue of Proceedings, reveals a dimerization interface between catalytic domains. We provide evidence here that FokI catalytic domain must dimerize for DNA cleavage to occur. First, we show that the rate of DNA cleavage catalyzed by various concentrations of FokI are not directly proportional to the protein concentration, suggesting a cooperative effect for DNA cleavage. Second, we constructed a FokI variant, FokN13Y, which is unable to bind the FokI recognition sequence but when mixed with wild-type FokI increases the rate of DNA cleavage. Additionally, the FokI catalytic domain that lacks the DNA binding domain was shown to increase the rate of wild-type FokI cleavage of DNA. We also constructed an FokI variant, FokD483A, R487A, which should be defective for dimerization because the altered residues reside at the putative dimerization interface. Consistent with the FokI dimerization model, the variant FokD483A, R487A revealed greatly impaired DNA cleavage. Based on our work and previous reports, we discuss a pathway of DNA binding, dimerization, and cleavage by FokI endonuclease.
Structure of FokI has Implications for DNA Cleavage Wah, David A.; Bitinaite, Jurate; Schildkraut, Ira ...
Proceedings of the National Academy of Sciences - PNAS,
09/1998, Letnik:
95, Številka:
18
Journal Article
Recenzirano
Odprti dostop
FokI is a member an unusual class of restriction enzymes that recognize a specific DNA sequence and cleave nonspecifically a short distance away from that sequence. FokI consists of an N-terminal DNA ...recognition domain and a C-terminal cleavage domain. The bipartite nature of FokI has led to the development of artificial enzymes with novel specificities. We have solved the structure of FokI to 2.3 angstrom resolution. The structure reveals a dimer, in which the dimerization interface is mediated by the cleavage domain. Each monomer has an overall conformation similar to that found in the FokI-DNA complex, with the cleavage domain packing alongside the DNA recognition domain. In corroboration with the cleavage data presented in the accompanying paper in this issue of Proceedings, we propose a model for FokI DNA cleavage that requires the dimerization of FokI on DNA to cleave both DNA strands.
Mainstream partial nitritation and Anammox (PN/A) has been observed and studied in the step-feed activated sludge process at the Changi water reclamation plant (WRP), which is the largest WRP ...(800,000 m3/d) in Singapore. This paper presents the study results for enhanced biological phosphorus removal (EBPR) co-existing with PN/A in the activated sludge process. Both the in-situ EBPR efficiency and ex-situ activities of phosphorus release and uptake were high. The phosphorus accumulating organisms were dominant, with little presence of glycogen accumulating organisms in the activated sludge. Chemical oxygen demand (COD) mass balance illustrated that the carbon usage for EBPR was the same as that for heterotrophic denitrification, owing to autotrophic PN/A conversions. This much lower carbon demand for nitrogen removal, compared to conventional biological nitrogen removal, made effective EBPR possible. This paper demonstrated for the first time the effective EBPR co-existence with PN/A in the mainstream in a large full-scale activated sludge process, and the feasibility to accommodate EBPR into the mainstream PN/A process. It also shows EBPR can work under warm climates.
FokI is a member of an unusual class of bipartite restriction enzymes that recognize a specific DNA sequence and cleave DNA nonspecifically a short distance away from that sequence. Because of its ...unusual bipartite nature, FokI has been used to create artificial enzymes with new specificities. We have determined the crystal structure at 2.8A resolution of the complete FokI enzyme bound to DNA. As anticipated, the enzyme contains amino- and carboxy-terminal domains corresponding to the DNA-recognition and cleavage functions, respectively. The recognition domain is made of three smaller subdomains (D1, D2 and D3) which are evolutionarily related to the helix-turn-helix-containing DNA-binding domain of the catabolite gene activator protein CAP. The CAP core has been extensively embellished in the first two subdomains, whereas in the third subdomain it has been co-opted for protein-protein interactions. Surprisingly, the cleavage domain contains only a single catalytic centre, raising the question of how monomeric FokI manages to cleave both DNA strands. Unexpectedly, the cleavage domain is sequestered in a 'piggyback' fashion by the recognition domain. The structure suggests a new mechanism for nuclease activation and provides a framework for the design of chimaeric enzymes with altered specificities.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background:
The evidence supporting best practice guidelines in the field of cartilage repair of the ankle are based on both low quality and low levels of evidence. Therefore, an international ...consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on Post-treatment Follow-up, Imaging and Outcome Scores developed at the 2017 International Consensus Meeting on Cartilage Repair of the Ankle.
Methods:
Seventy-five international experts in cartilage repair of the ankle representing 25 countries and 1 territory were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within 11 working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed and the available evidence for each statement was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterized as follows: consensus, 51% to 74%; strong consensus, 75% to 99%; unanimous, 100%.
Results:
A total of 12 statements on Post-treatment Follow-up, Imaging, and Outcome Scores reached consensus during the 2017 International Consensus Meeting on Cartilage Repair of the Ankle. All 12 statements reached strong consensus (greater than 75% agreement).
Conclusions:
This international consensus derived from leaders in the field will assist clinicians with post-treatment follow-up, imaging, and outcome scores after management of a cartilage injury of the ankle in the general population. Moreover, healing, rehabilitation, and final outcomes can be optimized for the individual patient.
We present a new determination of the parity of the neutral pion via the double Dalitz decay pi0-->e+e-e+e-. Our sample, which consists of 30,511 candidate decays, was collected from KL-->pi0pi0pi0 ...decays in flight at the KTeV-E799 experiment at Fermi National Accelerator Laboratory. We confirm the negative pi0 parity and place a limit on scalar contributions to the pi0-->e+e-e+e- decay amplitude of less than 3.3% assuming CPT conservation. The pi0gamma*gamma* form factor is well described by a momentum-dependent model with a slope parameter fit to the final state phase-space distribution. Additionally, we have measured the branching ratio of this mode to be B(pi0-->e+e-e+e-)=(3.26+/-0.18)x10(-5).
Objective To evaluate access site and other bleeding complications associated with radial versus femoral access in patients receiving oral anticoagulation (OAC) with warfarin. Background Patients ...receiving OAC with warfarin undergoing coronary angiography and percutaneous coronary intervention (PCI) may have OAC continued despite the risk of bleeding. To what extent arterial access site impacts bleeding in such patients is not well studied. Methods Over 6 years, we identified 255 consecutive patients in whom warfarin was continued who underwent coronary angiography with an international normalized ratio >1.8. A total of 97 patients also underwent PCI at the same setting (27% femoral vs 73% radial). The primary outcome was Bleeding Academic Research Consortium bleeds; a secondary end point was frequency of access site complications in the 72 hours post-PCI. Complications were evaluated based on the initial access site attempted. Results Minimal baseline clinical characteristics differences existed between the groups. International normalized ratio was significantly higher in the radial group (2.42 ± 0.67 vs 2.24 ± 0.49, P = .02). Bivalirudin use was greater during radial PCI than femoral (76% vs 42%, P < .05), whereas unfractionated heparin alone was greater during femoral PCI than radial (46% vs 18%, P < .05). No significant difference was seen in the primary end point between femoral (2.8%) and radial (1.6%, P = .54) during coronary angiography alone. However, PCI via the femoral artery had significantly more Bleeding Academic Research Consortium bleeding (19.2% vs 1.4%, P = .005) and transfusions (15% vs 0%, P = .004) than via the radial artery. Patients who underwent PCI using radial access were less likely to have any vascular or bleeding complications (1% vs 23%, P = .001). Conclusions Patients who underwent coronary angiography during uninterrupted OAC had similar bleeding rates regardless of access site. However, when PCI was performed, radial access was associated with fewer bleeding and vascular complications than the femoral approach. Condensed Abstract We retrospectively identified 255 consecutive patients on warfarin who underwent coronary angiography, 97 of whom underwent a percutaneous coronary intervention. The data reveal a reduction in Bleeding Academic Research Consortium bleeds (1.6% vs 8.1%, P = .02) with radial versus femoral access. The radial approach was associated with an overall lower rate of any vascular or bleeding complication than the femoral approach during percutaneous coronary intervention (1% vs 23%, P = .001).
Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. ...Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system - liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo.
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