In this work we consider local minimizers (in the topology of transport distances) of the interaction energy associated with a repulsive–attractive potential. We show how the dimensionality of the ...support of local minimizers is related to the repulsive strength of the potential at the origin.
OBJECTIVE:To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patientʼs safety.
BACKGROUND:The World ...Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available.
METHODS:In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization.
RESULTS:A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ± 0.05 to 1.00 ± 0.05 (relative change by 17%, P < 0.001).
CONCLUSIONS:The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patientʼs safety. Further studies should elucidate which PBM measures are most clinically and cost effective.
TRIAL REGISTRATION:PBM-Study ClinicalTrials.gov, NCT01820949
Abstract Introduction Ameloblastoma is a rare, benign odontogenic tumour associated with a high recurrence rate. It accounts for 1% of all tumours of the jaws. The purpose of this study was to ...compare the ameloblastoma recurrence rate according to the type of treatment: radical or conservative. Patients and methods All patients with a diagnosis of ameloblastoma between 1991 and 2013 were retrospectively identified in order to extract topographic, radiological, and histological data and the type of treatment: conservative (marsupialization, enucleation, curettage) or radical (segmental resection) and to compare the recurrence rate according to the type of treatment. Results Twenty-seven patients were included, managed by conservative treatment (CT) in 22 cases and radical treatment (RT) in 14 cases. The recurrence rate was 90.9% in the CT group and 9.1% in the RT group ( P = 0.025) with a mean follow-up of 56.2 months. Discussion The recurrence rate after conservative treatment was higher than that after radical treatment. These results are similar to those reported in the literature. The choice of treatment must be adapted to the macroscopic and histological characteristics of each tumour and to the patient.
Enzymes are highly specific biocatalysts, yet they can promote unwanted side reactions. Here we investigated the factors that direct catalysis in the enoyl-thioester reductase Etr1p. We show that a ...single conserved threonine is essential to suppress the formation of a side product that would otherwise act as a high-affinity inhibitor of the enzyme. Substitution of this threonine with isosteric valine increases side-product formation by more than six orders of magnitude, while decreasing turnover frequency by only one order of magnitude. Our results show that the promotion of wanted reactions and the suppression of unwanted side reactions operate independently at the active site of Etr1p, and that the active suppression of side reactions is highly conserved in the family of medium-chain dehydrogenases/reductases (MDRs). Our discovery emphasizes the fact that the active destabilization of competing transition states is an important factor during catalysis that has implications for the understanding and the de novo design of enzymes.
Oligodontia demands multidisciplinary management due to its repercussions on dentofacial growth. To place implants to realize implant-borne fixed denture, preimplant surgery may be necessary if bone ...volumes are insufficient. Our aim was to assess bone increase following autogenic bone grafting and to discuss prosthetic options. Twenty patients followed for oligodontia, who underwent bone grafting, were treated from 2008 to 2019. Transversal and vertical bone levels were measured pre- and postoperatively to assess alveolar ridge augmentation. Mean horizontal grafting increase was 4.60 mm standard deviation (SD) 0.79 mm, mean sinus lift increase was 9.95 mm (SD 2.35 mm). Mean implants placed per patient was 9, mean implants placed on grafted site was 5 per patient. Overall implant survival rate was 100%. All patients benefited from prosthetic procedures when it was planned to perform implant-borne fixed dentures. Within the framework of a complete treatment plan (involving paediatric dentistry, dentofacial orthopaedics, oral and maxillofacial surgery, and prosthodontics), autologous bone grafting combined or not with orthognathic surgery is fully adapted to patients with oligodontia. It allows reconstruction of favourable bone volumes for placement of implants to realize implant-borne fixed dentures, with high implant survival rates and great improvements to quality of life.
Mandibular reconstruction using fibula free flap has been improved in the last decade with computer-aided design and computer-aided manufacturing (CAD/CAM) but any functional and aesthetic evaluation ...of their reattempts has been realized. Aim of this retrospective study is to compare functional and morphologic outcomes after mandibular reconstruction with fibula free flap using CAD/CAM or conventional peroperative shaping for mandible reconstruction. Moreover, we compared quality of life, patient and surgery characteristics in the two groups.
We realized a monocentric retrospective analyzed of 25 cases of unilateral mandibular reconstruction divided in two groups, using CAD/CAM (12 patient) or conventional approach (13 patients) between April 2012 and March. Functional and aesthetic measurements were performed postoperatively.
Mouth opening, laterotrusion and protrusion of the mandible seemed to be improved in CAD/CAM group compared with conventional group but did not differ significantly. Quality of life, bite force, masticatory ability, eating and chewing satisfaction, appearance and social activity satisfaction did not differ significantly in the two groups.
Even if no superiority has been established for CAD/CAM group regarding functional and aesthetic outcomes, a prospective design of future studies and transdisciplinary approach should improve our data and their interpretations. Thus, the integration of virtual planning and guided surgery is definitely of significant value and must be considered in complex maxillofacial reconstructions.
The enoyl-thioester reductase InhA catalyzes an essential step in fatty acid biosynthesis of Mycobacterium tuberculosis and is a key target of antituberculosis drugs to combat multidrug-resistant M. ...tuberculosis strains. This has prompted intense interest in the mechanism and intermediates of the InhA reaction. Here, using enzyme mutagenesis, NMR, stopped-flow spectroscopy, and LC–MS, we found that the NADH cofactor and the CoA thioester substrate form a covalent adduct during the InhA catalytic cycle. We used the isolated adduct as a molecular probe to directly access the second half-reaction of the catalytic cycle of InhA (i.e. the proton transfer), independently of the first half-reaction (i.e. the initial hydride transfer) and to assign functions to two conserved active-site residues, Tyr-158 and Thr-196. We found that Tyr-158 is required for the stereospecificity of protonation and that Thr-196 is partially involved in hydride transfer and protonation. The natural tendency of InhA to form a covalent C2-ene adduct calls for a careful reconsideration of the enzyme’s reaction mechanism. It also provides the basis for the development of effective tools to study, manipulate, and inhibit the catalytic cycle of InhA and related enzymes of the short-chain dehydrogenase/reductase (SDR) superfamily. In summary, our work has uncovered the formation of a covalent adduct during the InhA catalytic cycle and identified critical residues required for catalysis, providing further insights into the InhA reaction mechanism important for the development of antituberculosis drugs.
An improved understanding of enzymes' catalytic proficiency and stereoselectivity would further enable applications in chemistry, biocatalysis and industrial biotechnology. We use a chemical probe to ...dissect individual catalytic steps of enoyl-thioester reductases (Etrs), validating an active site tyrosine as the cryptic proton donor and explaining how it had eluded definitive identification. This information enabled the rational redesign of Etr, yielding mutants that create products with inverted stereochemistry at wild type-like turnover frequency.
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