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Christophe, Thierry,Jackson, Mary,Jeon, Hee Kyoung,Fenistein, Denis,Contreras-Dominguez, Monica,Kim, Jaeseung,Genovesio, Auguste,Carralot, Jean-Philippe,Ewann, Fanny,Kim, Eun Hye,Lee, Sae Yeon,Kang, S Public Library of Science 2009 PLoS pathogens Vol.5 No.10
<▼1><P>A critical feature of <I>Mycobacterium tuberculosis</I>, the causative agent of human tuberculosis (TB), is its ability to survive and multiply within macrophages, making these host cells an ideal niche for persisting microbes. Killing the intracellular tubercle bacilli is a key requirement for efficient tuberculosis treatment, yet identifying potent inhibitors has been hampered by labor-intensive techniques and lack of validated targets. Here, we present the development of a phenotypic cell-based assay that uses automated confocal fluorescence microscopy for high throughput screening of chemicals that interfere with the replication of <I>M. tuberculosis</I> within macrophages. Screening a library of 57,000 small molecules led to the identification of 135 active compounds with potent intracellular anti-mycobacterial efficacy and no host cell toxicity. Among these, the dinitrobenzamide derivatives (DNB) showed high activity against <I>M. tuberculosis</I>, including extensively drug resistant (XDR) strains. More importantly, we demonstrate that incubation of <I>M. tuberculosis</I> with DNB inhibited the formation of both lipoarabinomannan and arabinogalactan, attributable to the inhibition of decaprenyl-phospho-arabinose synthesis catalyzed by the decaprenyl-phosphoribose 2′ epimerase DprE1/DprE2. Inhibition of this new target will likely contribute to new therapeutic solutions against emerging XDR-TB. Beyond validating the high throughput/content screening approach, our results open new avenues for finding the next generation of antimicrobials.</P></▼1><▼2><P><B>Author Summary</B></P><P>Tuberculosis is still a major threat to global health. The disease in humans is caused by a bacterium, <I>Mycobacterium tuberculosis</I>, and treatment of an infected individual requires more than six months of chemotherapy. Because such a long course of treatment is required, compliance is low, which can result in the development of multidrug resistant strains (MDR-TB) and even extremely resistant strains (XDR-TB). Identifying new drug targets and potential lead therapeutic compounds are needed to combat MDR-XDR-TB. We developed a new type of assay based on the visualization of mycobacterium replication within host cells and applied it for the search of compounds that are able to chase the pathogen from its hideout. As a result, we found 20 new series of drug candidates that are effective against the bacilli in its hiding place, potentially addressing a crucial aspect in the resilience of the disease. We also showed that one series of compounds acts by inhibiting a key enzyme required for the synthesis of an essential component from the mycobacterial cell wall that is not targeted by any of the commercially available antituberculosis drugs. Altogether, our results pave the way for development of the next generation of antibacterial agents.</P></▼2>
Challenges and Future of Wireless Capsule Endoscopy
Jean-Christophe Saurin,Nicolas Beneche,Christine Chambon,Mathieu Pioche 대한소화기내시경학회 2016 Clinical Endoscopy Vol.49 No.1
In 2015, capsule endoscopy was introduced as the main investigation method for small bowel mucosal diseases, and its role in colonic diseases has been gradually revealed. Future challenges for capsule endoscopy, besides improvements of image quality and visualization of each part of the small bowel and colonic mucosa, include the development of gastric capsules, the capacity to perform histological examination of the mucosa, and maybe in the future, some capsule endoscopy-driven therapeutics. The aim of this review was to evaluate the clinical demands and feasibility of achieving the aforementioned objectives.
WFUMB position paper on the management incidental findings: adrenal incidentaloma
Christoph F. Dietrich,Jean Michel Correas,Yi Dong,Christian Nolsoe,Susan Campbell Westerway,Christian Jenssen 대한초음파의학회 2020 ULTRASONOGRAPHY Vol.39 No.1
Focal lesions of the adrenal glands are incidentally detected in approximately 5% of cases by modern imaging techniques. Fewer than 5% of these adrenal incidentalomas are malignant and approximately 10% have endocrine activity. Reliable differentiation of malignant versus benign and hormonally active versus nonfunctional adrenal incidentalomas significantly influences therapeutic management and the outcome of affected individuals. Therefore, each adrenal incidentaloma should undergo a standardized diagnostic work-up to exclude malignancy and endocrine activity. This position statement of the World Federation of Ultrasound in Medicine and Biology (WFUMB) summarizes the available evidence on the management of adrenal incidentaloma and describes efficient management strategies with particular reference to the role of ultrasound techniques.
Jean-Charles Hery,Baptiste Picart,Mélanie Malherbe,Christophe Hulet,Aude Lombard 대한성형외과학회 2021 Archives of Plastic Surgery Vol.48 No.6
Background Injuries to the proximal interphalangeal (PIP) joint are common and complex. However, the treatment of osteochondral defects of the head of the proximal phalanx has rarely been described. Herein, we propose a new technique for the management of unicondylar defects of the proximal phalanx that can restore joint amplitudes and provide PIP stability. Methods In this cadaveric feasibility study, unicondylar defects were generated using striking wedges and chisels. First, a transverse tunnel measuring 2 mm in diameter passing through the head of the proximal phalanx was made. A second tunnel at the base of the middle phalanx with the same diameter was then created. The hemitendon of the flexor carpi radialis graft was passed through each of these tunnels. The proximal end of the graft was interposed in the area with a loss of bone substance. The ligamentoplasty was then tensed and fixed by two anchors on the proximal phalanx. Joint amplitudes and frontal stability were measured preoperatively and postoperatively. Results There was no significant change in the joint’s range of motion: preoperatively, the mean mobility arcs were –2° to 113.80°, and they were –2° to 110° after the procedure (P= 0.999). There was no significant difference in joint stability (P>0.05). Conclusions Ligamentoplasty with PIP interposition appears to be a possible solution for the management of unicondylar defects of the proximal phalanx. An evaluation of clinical results is planned in order to definitively confirm the validity of this procedure.
CONTRIBUTIONS OF THE VULCANO EXPERIMENTAL PROGRAMME TO THE UNDERSTANDING OF MCCI PHENOMENA
Christophe, Journeau,Piluso, Pascal,Correggio, Patricia,Ferry, Lionel,Fritz, Gerald,Haquet, Jean Francois,Monerris, Jose,Ruggieri, Jean-Michel,Sanchez-Brusset, Mathieu,Parga, Clemente Korean Nuclear Society 2012 Nuclear Engineering and Technology Vol.44 No.3
Molten Core Concrete Interaction (MCCI) is a complex process characterized by concrete ablation and volatile generation; Thermal and solutal convection in a bubble-agitated melt; Physico-chemical evolution of the corium pool with a wide solidification range (of the order of 1000 K). Twelve experiments have been carried out in the VULCANO facility with prototypic corium and sustained heating. The dry oxidic corium tests have contributed to show that silica-rich concrete experience an anisotropic ablation. This unexpected ablation pattern is quite reproducible and can be recalculated, provided an empirical anisotropy factor is assumed. Dry tests with oxide and metal liquid phases have also yielded unexpected results: a larger than expected steel oxidation and unexpected topology of the metallic phase (at the bottom of the cavity and also on the vertical concrete walls). Finally, VULCANO has proved its interest for the study of mitigation solutions such as the COMET bottom flooding core catcher.
Nicolet, Christophe,Alligne, Sebastien,Kawkabani, Basile,Simond, Jean-Jacques,Avellan, Francois Korean Society for Fluid machinery 2009 International journal of fluid machinery and syste Vol.2 No.4
This paper presents a numerical simulation study of the transient behavior of a $2{\times}340MW$ pump-turbine power plant, where the results show an unstable behavior at runaway. First, the modeling of hydraulic components based on equivalent schemes is presented. Then, the 2 pump-turbine test case is presented. The transient behavior of the power plant is simulated for a case of emergency shutdown with servomotor failure on Unit 1. Unstable operation at runaway with a period of 15 seconds is properly simulated using a 1-dimensional approach. The simulation results points out a switch after 200 seconds of the unstable behavior between a period of oscillations initially of 15 seconds to a period of oscillation of 2.16 seconds corresponding to the hydraulic circuit first natural period. The pressure fluctuations related to both the rigid and elastic water column mode are presented for oscillation mode characterization. This phenomenon is described as a switch between a rigid and an elastic water column oscillation mode. The influence of the rotating inertia on the switch phenomenon is investigated through a parametric study.
Anterior Bone Loss in Cervical Disc Arthroplasty
David Christopher Kieser,Derek Thomas Cawley,Takashi Fujishiro,Celeste Tavolaro,Simon Mazas,Louis Boissiere,Ibrahim Obeid,Vincent Pointillart,Jean Marc Vital,Olivier Gille 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.1
Study Design: Retrospective, longitudinal observational study. Purpose: To describe the natural history of anterior bone loss (ABL) in cervical disc arthroplasty (CDA) and introduce a classification system for its assessment. Overview of Literature: ABL has recently been recognized as a complication of CDA, but its cause and clinical effects remain unknown. Methods: Patients with non-keeled CDA (146) were retrospectively reviewed. X-rays were examined at 6 weeks, 3, 6, 9, 12, 18, and 24 months, and annually thereafter for a minimum of 5 years. These were compared with the initial postoperative X-rays to determine the ABL. Visual Analog Scale pain scores were recorded at 3 months and 5 years. Neck Disability Index was recorded at postoperative 5 years. The natural history was determined and a classification system was introduced. Results: Complete radiological assessment was available for 114 patients with 156 cervical disc replacements (CDRs) and 309 endplates (average age, 45.3 years; minimum, 28 years; maximum, 65 years; 57% females). ABL occurred in 57.1% of CDRs (45.5% mild, 8.3% moderate, and 3.2% severe) and commenced within 3 months of the operation and followed a benign course, with improvement in the bone stock after initial bone resorption. There was no relationship between ABL degree and pain or functional outcome, and no implants were revised. Conclusions: ABL is common (57.1%). It occurs at an early stage (within 3 months) and typically follows a non-progressive natural history with stable radiographic features after the first year. Most ABL cases are mild, but severe ABL occurs in approximately 3% of CDAs. ABL does not affect the patients’ clinical outcome or the requirement for revision surgery. Surgeons should thus treat patients undergoing CDA considering ABL.