Littérature scientifique sur le sujet « MRT-92 »

Abstract Introduction Allogeneic hematopoïetic stem cell transplantation (HSCT) is the only established curative therapy for patients (pts) with sickle cell disease (SCD). It is mostly performed in children 1, due to higher risk of graft-versus-host disease (GVHD) and transplant related mortality in adults. Different approaches have been developped to improve tolerance of transplant in adults: use of reduced intensity conditioning (RIC) regimens 2 and intensive immunosuppression to avoid GVHD. Here, we have studied the impact of such approaches on immune reconstitution in adolescents and adults transplanted for SCD. Patients and methods We report 39 transplants in adolescents and adults, performed in Saint Louis hospital from 2008 to 2020: 25 were matched related transplants (MRT) and 14 haplo-identical related transplant (HRT). In MRT, conditioning was myeloablative (MAC) in 15 pts (busulfan, cyclophosphamide, rabbit anti-thymoglobulin (ATG) 20 mg/kg) and non myeloablative (NMA) in 10 pts (alemtuzumab 1 mg/kg, 3 Gy total body irradiation (TBI)). In MAC transplants, stem cell source was bone marrow and post-transplant immunosuppression was methotrexate and cyclosporine. In NMA transplants, stem cell source was peripheral blood cells with post-transplant immunosuppression by sirolimus. In the 14 HRT, the conditioning was reduced (cyclophosphamide, thiotepa, fludarabine, 2 Gy TBI, ATG 4.5 mg/kg), stem cell source was bone marrow and GVHD prophylaxis was ensured by post-transplant cyclophosphamide (100 mg/kg), sirolimus and mycophenolate mofetil. Results Median age at transplant was 17 years (y) old (range (r) 14-39). With a median follow-up of 3.6 y, the 2-y overall survival and survival without SCD were 97% (IC95%: 0.92-1) and 92% (IC95%: 0.83-1) respectively: no event after MRT, 1 death of GVHD and 2 graft rejections after HRT. The acute GVHD grade II-IV rate was 33%: 21% after HRT, 13% after MAC MRT and 0% after NMA MRT. Chronic GVHD occured in 3 pts (8%): severe in 1 HRT and mild in 2 MAC MRT. At 6 months, the blood chimerism evaluated in the 36 patients alive without rejection, was more often mixed (5 to 95% of donor) after NMA MRT (100%) versus MAC MRT (40%, p = 0.003) and HRT (18%, p < 0.001). Total lymphocytes (TL) counts increased rapidly in HRT and MAC MRT with a normalization from 3 months post-transplant. In contrast, NMA MRT experienced a slower recovery: at 6 months, median count was 1039/mm3 (r 463-1767) compared to 2071/mm3 (r 882-5985, p = 0.002) after MAC MRT and 2382/mm3 (r 676-3978, p = 0.005) after HRT. After NMA MRT, TL counts remained lower than normal values up to 12 months with a median of 1195/mm3 (r 870-3210) (Figure 1A). HRT displayed a rapid normalization of CD4 counts with a 3-month median count of 645/mm3 (r 350-1076) higher than reported after MRT (p < 0.001). Evolution of CD4 counts was similar after NMA and MAC MRT. They were lower than normal values during the first 12 months: median 364/mm3 and 388/mm3 respectively at 12 months (p = 0.25) (Figure 1B). From 3 months post-transplant, CD8 counts reached normal values after MAC MRT (314/mm3, r 108-2175) and were superior to normal after HRT (1335/mm3, r 66-4529), with a significant difference between HRT and MRT (p = 0.003). After NMA MRT, there was a trend for lower 3-month CD8 counts compared to MAC MRT: median of 107/mm3 (r 18-631, p = 0.08). CD8 counts remained under normal values after NMA MRT up to 12 months post-transplant (Figure 1C). From 3 to 6 months, CD4 and CD8 were mostly memory, with only 3.2% (r 0.1%-20.6%) and 6.2% (r 2.1%-11.2%) of CD45RA+ CCR7+ naïve CD8+ and CD4+ respectively. In the 3 groups NK cell counts reached normal values after 3 months. B lymphocytes counts normalized in the first months post-transplant except for patients who received rituximab for EBV reactivation. From 3 to 6 months, B lymphocytes were mostly naive: 98% of CD27- (r 92%-99%). Gammaglobuline levels were normal from 3 months in the 3 groups. Twelve (31%) pts were treated for a CMV and 6 (15%) for an EBV reactivation. No patient had CMV or adenovirus disease, or post-transplant lymphoproliferative disorder. Infections according to transplant types are detailed in figure 1D. Conclusion NMA MRT were associated with a delayed CD4 and CD8 recovery probably due to alemtuzumab. As previously reported 3, HRT displayed a rapid immune reconstitution. Despite use of serotherapy in the three modalities of transplant, the rate of viral infections remained acceptable without severe episode. Figure 1 Figure 1. Disclosures Pondarré: ADDMEDICA: Honoraria. Peffault De Latour: Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Amgen: Consultancy, Other, Research Funding; Alexion, AstraZeneca Rare Disease: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding. Boissel: CELGENE: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; JAZZ Pharma: Honoraria, Research Funding; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Servier: Consultancy, Honoraria; SANOFI: Honoraria; PFIZER: Consultancy, Honoraria.

AbstractWe report on new molecular-line observations of the bipolar pre-planetary nebula M 1–92. The new IRAM 30 m MRT and NOEMA data shows the presence of shock induced chemistry in the nebula. From the derived [17O]/[18O] ratio, we suggest that the sudden mass loss event responsible for the formation of the nebula 1200 yr ago may also have resulted in the premature end of the AGB phase of the central star.

Objective. To assess the variability of the anterolateral ligament according to MRT and ultrasonography data and to coordinate it with surgical treatment strategy for its injuries. Methods. The anterolateral ligament was analyzed on 100 series of MRI images of knee joints without traumatic pathology on Philips Achieva 1.5 T tomograph using the standard research protocol in three mutually perpendicular planes and 150 series of MRT images of knee joints with injuries and without injuries of the anterolateral ligament obtained on different tomographs from 0.2 to 3 Tesla. The quality of visualization of anterolateral ligament separate portions, the number of layers, and the contact with the joint capsule were evaluated. Both knee joints were analyzed by ultrasonography in 30 patients with anterior cruciate ligament injuries of one of the knee-joint and in 30 patients with intact knee-joints. Results. During the studies in the identification of anterolateral ligament with magnetic resonance tomography (MRT 1.5T)it was revealed at least partially in 92% of cases (in 68% as a two-layer structure; in 24% as a single-layer structure; in 14% as a thickening of the capsule or in 10% as a separate extracapsular structure), ultrasound examination - in 100% (the structure was not determined, however, in 26.67% of patients without clinically pronounced pathology of the knee-joint and significant trauma in anamnesis ultrasound scan revealed a violation of the integrity of the cortical layer at the tibial attachment site), Conclusion. According to MRT and ultrasonography data, the anterolateral ligament is a constant structure of the knee-joint, but very variable in its anatomical parameters, which in some cases may be poorly visualized on MRT, may have a two-layer structure, may be located either extracapsular or as a thickening of the knee-joint capsule. The variability of its anatomical structure makes it impossible to make the theoretical substantiation of the advantages of one separate method of its restoration, but, on the contrary, justifies a differentiated approach to the selection of optimal surgical treatment. What this paper adds With the help of current research methods, the normal anatomical parameters and anatomical variants of the anterolateral ligament of the knee joint have been clarified and detailed. It is necessary to emphasize the importance of a differentiated approach to choosethe optimal methods of surgical treatment for its injuries.

Purpose:To assess whether combining prior “priming” exercise with an all-out pacing strategy is more effective at improving oxygen-uptake (V̇O2) kinetics and cycling performance than either intervention administered independently.Methods:Nine men completed target-work cycling performance trials using a self-paced or all-out pacing strategy with or without prior severe-intensity (70%Δ) priming exercise. Breath-by-breath pulmonary V̇O2 and cycling power output were measured during all trials.Results:Compared with the self-paced unprimed control trial (22 ± 5 s), the V̇O2 mean response time (MRT) was shorter (V̇O2 kinetics were faster) with all-out pacing (17 ± 4 s) and priming (17 ± 3 s), with the lowest V̇O2 MRT observed when all-out pacing and priming were combined (15 ± 4 s) (P < .05). However, total O2 consumed and end-exercise V̇O2 were only higher than the control condition in the primed trials (P < .05). Similarly, cycling performance was improved compared with control (98 ± 11 s) in the self-paced primed (93 ± 8 s) and all-out primed (92 ± 8 s) trials (P < .05) but not the all-out unprimed trial (97 ± 5 s; P > .05).Conclusions:These findings suggest that combining an all-out start with severe-intensity priming exercise additively improves V̇O2 MRT but not total O2 consumption and cycling performance since these were improved by a similar magnitude in both primed trials relative to the self-paced unprimed control condition. Therefore, these results support the use of priming exercise as a precompetition intervention to improve oxidative metabolism and performance during short-duration high-intensity cycling exercise, independent of the pacing strategy adopted.

Zielsetzung Ziel dieser Studie war die Evaluierung des prädiktiven Potenzials der Radiomics-Analyse zur Bestimmung des N- und M-Stadiums des primären Zervixkarzinoms anhand multiparametrischer 18F-FDG-PET/MRT-Bildgebung. Material und Methoden 30 Patientinnen mit einem histologisch gesicherten, primären und therapienaiven Zervixkarzinom unterzogen sich einer multiparametrischen 18F-FDG-PET/MRT-Untersuchung unter Verwendung eines dedizierten Untersuchungsprotokolls des weiblichen Beckens. Nach Segmentierung der Primärtumoren wurden quantitative Bildparameter mittels der Radiomic-Image-Processing-Toolbox bestimmt. Insgesamt wurden 45 verschiedene quantitative Bildmerkmale jeweils anhand der T2-gewichteten TSE-Sequenzen, der nativen und kontrastmittelgestützten T1-gewichteten TSE-Sequenzen, der ADC-Map, verschiedenen Perfusionsparametern (Ktrans, Kep, Ve and iAUC) und den 18F-FDG-PET-Datensätzen für jeden Tumor extrahiert. Die statistische Analyse zur Bestimmung des N- und M-Stadiums erfolgte unter der Verwendung der Python 3.5 und Scikit-learn-Software-Bibliothek für maschinelles Lernen. Ergebnisse Insgesamt zeigte sich eine höhere Genauigkeit zur Prädiktion des korrekten M-Stadiums im Vergleich zum N-Stadium. Zur Prädiktion des korrekten M-Stadiums zeigten sich unter der Verwendung von SVM und SVM-RFE zur Feature-Auswahl die besten Ergebnisse mit einer Sensitivität von 91 %, einer Spezifität von 92 % und einer Fläche unter der Kurve (AUC) von 0,97. Die höchste Genauigkeit für die Bestimmung des N-Stadiums erfolgte unter der Verwendung von RBF-SVM und MIFS zur Feature-Auswahl mit einer Sensitivität von 83 %, einer Spezifität von 67 % und einer Fläche unter der Kurve (AUC) von 0,82. Schlussfolgerung Die Radiomics-Analyse von multiparametrischen PET/MR-Datensätzen ermöglicht eine präzise Prädiktion des M- und N-Stadiums von Patientinnen mit primärem Zervixkarzinom und könnte damit supportiv zur nichtinvasiven Tumor-Phänotypisierung und Patientenstratifizierung eingesetzt werden. Kernaussagen: Citation Format

Zusammenfassung Hintergrund In den Leitlinien onkologischer Krankheitsbilder wird zur bildgebenden Diagnostik vorrangig ein PET-CT, CT und MRT gefordert. Der Stellenwert der Sonografie ist unklar. Fragestellung Ziel der Arbeit ist es, den Stellenwert des Ultraschalls in der Hämatologie und Onkologie in einem universitären interdisziplinären Ultraschallzentrum zu analysieren. Material und Methoden Von Januar bis April 2017 wurden 5019 Ultraschalluntersuchungen durchgeführt. In n = 1506 (30 %) Fällen lag eine hämatologische (H) oder onkologische (O) Problemstellung vor. Die retrospektive Auswertung der Ultraschallanforderungen und Ultraschallbefunde erfolgte hinsichtlich: 1. H/O-Fragestellung, 2. Zuweiser, 3. Untersuchungsmodalität, 4. Organuntersuchung, und 5. Klinischer Hintergrund. Ergebnisse H/O-Fragestellung betrafen: Screeninguntersuchungen (165; 11 %), Primärdiagnostik (508; 34 %), Ausbreitungsdiagnostik (92; 6 %), Therapieansprechen (264; 18 %), Nachsorge (100; 7 %) und akute Probleme (377; 25 %). Die untersuchten Fälle waren ambulant (675; 44,8 %) oder stationär (831; 55,2 %). Neben dem B-Bild Ultraschall (100 %) kamen kontrastmittelunterstützte Sonografie (162; 11 %) und Interventionen (79; 5 %) zum Einsatz. Ultraschalluntersuchungen des Abdomens wurden am häufigsten angefordert (1033; 69 %). Diskussion Diese unizentrische Studie zeigt, dass Ultraschalldiagnostik einen breiten Einsatz bei hämatologischen und onkologischen Patienten einnimmt. Die größte Bedeutung des Ultraschalls liegt in der primären Tumordiagnostik und bei akuten Therapie- und/oder erkrankungsassoziierten Komplikationen.

The study was conducted to observe the overall seroprevalence and molecular detection of circulating FMD virus from infected cattle and efficacy of antibacterial drugs against secondary bacterial infection at Savar, Dhaka from January- December 2018. A total of 92 serum samples were collected for indirect c-ELISA to detect antibodies against non-structural proteins of FMD virus, and overall seroprevalence was 94.02%. The seroprevalence of serotype O and A was higher (95.83% and 95.83%) in male cattle than female (93.18% and 90.91%) respectively. 6 Months to 3 years aged cattle showed, significantly (p<0.01) higher seroprevalence (100%) than above 4 years age groups for serotype O (82.14%) and A (78.57%). Local cattle were more seropositive 96.88% compared to crossbred cattle 93.33% for serotype O and 91.67% for serotype A and this variation was not statistically significant (p>0.05). Among 10 clinical samples of FMD from infected cattle, 8 samples were positive for different serotypes, among them 2 each were identified as serotype A and Asia-1. On the other hand,4 samples were identified as mixed infection (1 sample of serotype O+A, 3 samples of O+Asia-1) by mRT-PCR. In this study on therapeutic intervention with sulphadimidine significantly (p<0.05) reduced the clinical signs of FMD than Gentamycin and Ampicillin. The higher seroprevalence of the disease has substantial economic implications which signify the need for devising effective control measure. However, the detection of ‘O’, Asia-1and ‘A’ serotype emphasizes the critical need for use of atrivalent vaccine in the field. SAARC J. Agri., 17(2): 67-78 (2019)

Amitraz, a member of the formamidine pesticide family, commonly used for ectoparasite control, is applied as a dip or low-pressure hand spray to cattle and swine, and the neck collar on dogs. Data on amitraz were generated mainly on laboratory animals, hens, dogs, and baboons. The data on the toxicity and disposition of amitraz in animals and its residues in the milk are inadequate. Therefore, the present study was intended to analyze the disposition kinetics of amitraz and its pattern of elimination in the milk of lactating does after a single dermal application at a concentration of 0.25%. Blood at predetermined time intervals and milk twice daily were collected for eight days post application. The drug concentration was assayed by high-performance liquid chromatography (HPLC). Amitraz was detected in whole blood as early as 0.5 h, which attained a peak concentration at 12 ± 5 h, followed by a steady decline; however, detection persisted until 168 h. Amitraz was present in the blood at its 50% Cmax even after 48 h, and was still detectable after 7 days. The disposition after a single dermal application was best described non-compartmentally. The mean terminal half-life (t1/2), mean residence time (MRT), and area under the curve (AUC0–t) were 111 ± 31 h, 168 ± 39 h, and 539 ± 211 µg/mL/h, respectively. The apparent volume of distribution (Vdarea) was 92 ± 36 mL/g with an observed clearance (Cl) of 0.57 ± 0.33 mL/kg/h. Thus, the drug was well absorbed, widely distributed and slowly eliminated from the animal body. Amitraz achieved milk concentration approximating 0.2 per cent of the total dose after a single exposure and the steady-state elimination of amitraz in milk above the recommended maximum residue limit (MRL) of 0.01 mg/kg can act as a source of public health concern when applied on lactating animals.

This study examines the effect of the porch on the adaptive thermal comfort of mosques by taking 2 mosques that have different porch shapes with the specific purpose of obtaining data on the neutrality, acceptability and preferences of the mosque respondents' thermal conditions in the framework of developing adaptive thermal comfort standards for Indonesia. Measurement of physical environment variables is done by taking data on temperature, humidity, air velocity, and mean radiant temperature (MRT) at 2 mosques and at the same time the impression and thermal preference questionnaire data are taken, examination of clothing types and activities, and list of thermal environment controls to 40 respondents in each mosque. Data of thermal neutrality and thermal preferences were analyzed by regression analysis using SPSS 19 software, while thermal acceptance was analyzed based on the results of the questionnaire answers. The analysis showed that the neutrality value at Ulul Albab mosque was Tdb = 28.47 OC, ET * = 30.11 OC, SET * = 23.11 OC, TSENS = 1.17, DISC = -1.06, and PMV = -0.65, this data shows that the neutral condition desired by respondents is slightly below the average condition, while the neutrality in Nurul Ilmi mosque at Tdb = 30.27 OC, ET * = 31.65 OC, SET * = 29.05 OC, TSENS = 1.03, DISC = 1.68, and PMV = 1.22, this data also shows that the neutral conditions desired by respondents are slightly below average conditions. While the preference value at Ulul Albab mosque is Tdb = 22.25 OC, ET * = 28.62 OC, SET * = 24.24 OC, TSENS = 0.23, DISC = 0.23, and PMV = -0.60 and preference conditions at Nurul Ilmi mosque at Tdb = 29.11 OC, ET * = 31.17 OC, SET * = 28.50 OC, TSENS = 1.04, DISC = 1.45, and PMV = 1.03. As many as 92% of respondents in the Ulul Albab mosque can accept local thermal conditions in the temperature range of 27oC - 31oC. While 90% of respondents in the Nurul Ilmi mosque can accept local thermal conditions in the temperature range of 27oC-32oC. The results of the neutrality, acceptance and preference analysis show that the Ulul Albab mosque is better than the Nurul Ilmi mosque.

This PhD project is focused on the improvable potency of small molecules to restore and reactivate the physiological functions of specific cellular signaling pathways involved in the development of serious and degenerative diseases, such as skin cancer, leukemia, neurodegenerative diseases. Hence, here is reported the synthesis and the biological evaluation of the Hedgehog pathway's agonists and antagonists, as well as the MRN Complex inhibitors. Moreover, we worked in the field of the bioconjugation with the synthesis of the so called molecular linkers, which have been then used to conjugate some known cytotoxic agents. The resulting payloads have been sent to prepare new Antibody Drug Conjugates (ADC) using specific monoclonal antibodies (mAbs)