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Melis, Eszter. « Átmenet a felnőttkorba : A gyermekek helyzete a középső bronzkorban Magyarország nyugati területein ». Magyar Régészet 12, no 3 (2023) : 14–26. http://dx.doi.org/10.36245/mr.2023.3.2.
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Az utóbbi néhány évtizedben került előtérbe a gyermekek helyzetének és szerepének vizsgálata a különböző történelmi és történelem előtti korokban. A sajnálatos módon gyermekkorukban elhunytak sírjai az egyik leggazdagabb és legfontosabb forrásanyagot jelentik a téma őskori kutatásához, amely a modern természettudományos vizsgálatoknak köszönhetően nemcsak a fiatalon elhunytak betegségeiről vagy neméről, hanem életmódjáról (pl. táplálkozásáról) is információval szolgálhat. Nem szabad azonban elfeledkeznünk arról, hogy a gyermekek eltemetésének módja, mellékleteik elsősorban a felnőttek közösségének a legfiatalabbakhoz, valamint elvesztésükhöz és a gyászhoz való viszonyát tárja fel. A Kr. e. 2200/2100–1600/1500 közötti periódus Magyarországon a kora bronzkor vége és a középső bronzkor időszaka. Ebben az időben a nyugatmagyarországi régióban húzódott a csontvázasan temetkező közép-európai Aunjetitz- és a rokon kultúrák (pl. Gáta–Wieselburg), valamint a hamvasztásos rítusú Kárpát-medencei csoportok (Kisapostag és Mészbetétes kerámia kultúrája) határterülete. A feltárt temetkezéseik 30–40%-ában gyermekek nyugodtak; a maradványok régészeti elemzése – bár korlátozottan – adhat arra választ, milyen lehetett a bronzkorban gyermeknek lenni, egyben a 3500–4000 évvel ezelőtti társadalmi szerveződés fontos aspektusait tárhatja fel előttünk.
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Kirkness, E. F., et A. J. Turner. « The γ-aminobutyrate/benzodiazepine receptor from pig brain. Purification and characterization of the receptor complex from cerebral cortex and cerebellum ». Biochemical Journal 233, no 1 (1 janvier 1986) : 265–70. http://dx.doi.org/10.1042/bj2330265.
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The gamma-aminobutyrate/benzodiazepine-receptor complex has been purified from a Triton X-100 extract of crude synaptic membranes from pig cerebral cortex and cerebellum by a combination of affinity and ion-exchange chromatography. [3H]Flunitrazepam binding activity was purified 2200-fold from cortex with an overall yield of 2%. The dissociation constants for the binding of [3H]muscimol and [3H]flunitrazepam to the receptor complex were 14 +/- 3 nM and 14 +/- 2 nM respectively. The ratio of [3H]muscimol to [3H]flunitrazepam binding sites was in the range 2.2-2.8. There appeared to be no selective inactivation of either binding site during the purification procedure. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis revealed two major polypeptides of Mr 49 000 and 55 000 from both cortex and cerebellum. When the receptor from cortex was photoaffinity labelled with [3H]flunitrazepam, radioactivity was incorporated predominantly into the Mr-49 000 polypeptide, although some radioactivity was detectable in the Mr-55 000 band. The cerebellar receptor was photoaffinity labelled on the 49 000-Mr polypeptide but not on the polypeptide of Mr 55 000. In addition, some radioactivity was detected in a minor polypeptide of Mr 43 000. When purified in the presence of 3-[(3-cholamidopropyl)dimethylammonio]propanesulphonate the same major polypeptide components (Mr 49 000 and 55 000) were isolated, but the receptor now retained its ability to be modulated by secobarbital and by the anaesthetic propanidid.
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Mattsson, Cecilia, Rebecca M. Reynolds, Kotryna Simonyte, Tommy Olsson et Brian R. Walker. « Combined Receptor Antagonist Stimulation of the Hypothalamic-Pituitary-Adrenal Axis Test Identifies Impaired Negative Feedback Sensitivity to Cortisol in Obese Men ». Journal of Clinical Endocrinology & ; Metabolism 94, no 4 (1 avril 2009) : 1347–52. http://dx.doi.org/10.1210/jc.2008-2054.
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Abstract Context: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline, and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR). Objective: The objective of the study was to use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity. Design: This was a double-blind, placebo-controlled, randomized, crossover study. Setting: The study was conducted at a clinical research facility. Participants: Participants included 15 lean (body mass index 22.0 ± 1.6 kg/m2) and 16 overweight/obese (body mass index 30.1 ± 3.5 kg/m2) men. Intervention: Subjects attended on four occasions for blood and saliva sampling every 30 min between 1800 and 2200 h. At 1100 and 1600 h before visits, subjects took 200 mg spironolactone, 400 mg RU38486, 200 mg spironolactone + 400 mg RU38486, or placebo orally. Main Outcome Measures: Serum cortisol levels after drug or placebo were measured. Results: Cortisol levels did not differ between lean and obese after placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by less than 50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, more so in lean than obese men [2.9- (0.3) vs. 2.2 (0.3)-fold elevation, P = 0.002]. Conclusions: Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.
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Choy, Francis Y. M., et Mary Woo. « Purification and the effect of peptide N-glycosidase F on lysosomal membrane-bound glucocerebrosidase from human cultured fibroblasts ». Biochemistry and Cell Biology 69, no 8 (1 août 1991) : 551–56. http://dx.doi.org/10.1139/o91-081.
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Glucocerebrosidase was purified from human cultured dermal fibroblasts more than 2200-fold to apparent homogeneity using high performance Alkyl-Superose HR 5/5 hydrophobic interaction and Bio-Sil TSK-250 gel permeation column chromatography. Sodium dodecyl sulfate – polyacrylamide gel electrophoresis and protein staining of the catalytically active and concentrated enzyme fractions from the gel permeation columns revealed the presence of one band of Mr 64 000. The glucocerebrosidase preparation purified to homogeneity was digested with peptide N-glycosidase F that cleaves N-linked oligosaccharide structures from glycoproteins. The molecular weight of glucocerebrosidase after digestion with peptide N-glycosidase F was reduced to Mr 57 000, suggesting that the mature enzyme is a glycoprotein and that N-linked oligosaccharide constitutes a minimum of about 10% of the total molecular weight of the polypeptide. These findings are compatible with the hypothesis that glucocerebrosidase was initially synthesized as a precursor polypeptide which was subsequently glycosylated to become the mature enzyme.Key words: glucocerebrosidase, purification, deglycosylation, N-glycosidase F, fibroblasts.
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Yang, Yi, Xianfu Luo, Fuhua Yan, Zheng Jiang, Yong Li, Chen Fang et Junkang Shen. « Effect of zoledronic acid on vertebral marrow adiposity in postmenopausal osteoporosis assessed by MR spectroscopy ». Skeletal Radiology 44, no 10 (1 juillet 2015) : 1499–505. http://dx.doi.org/10.1007/s00256-015-2200-y.
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Nemcsik-Bencze, Zsófia, Szabolcs Várbíró, Gábor Rudas et János Nemcsik. « Az izolált septum pellucidum hiány praenatalis diagnosztikája ultrahang- és mágneses rezonancia képalkotó vizsgálattal ». Orvosi Hetilap 161, no 52 (27 décembre 2020) : 2195–200. http://dx.doi.org/10.1556/650.2020.31912.
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Összefoglaló. A septoopticus dysplasia, vagy más néven De Morsier-szindróma egy ritka, az agy középvonali képleteit érintő rendellenesség, mely a septum pellucidum hiányával, hypophysis-diszfunkcióval, látóideg-hypoplasiával és mentális visszamaradottsággal jár együtt. A septum pellucidum hiánya önmagában is előfordulhat izolált formában, de ennek septoopticus dysplasiától való praenatalis elkülönítése jelentős diagnosztikai kihívást jelent. Az izolált septum pellucidum hiány a kevés, rendelkezésünkre álló irodalmi adat alapján ártalmatlan anatómiai variáció. Esetbemutatásunkban a magas mágneses térerővel végzett magzati mágneses rezonancia (MR) képalkotó vizsgálat segítette az izolált septum pellucidum hiány septoopticus dysplasiától való elkülönítését azáltal, hogy lehetővé tette a látóidegek és a chiasma pontosabb megítélését, valamint az esetleges egyéb agyi rendellenességek kizárását. A szülés utáni kétéves követési periódus alatt a gyermek normális szomatomentális fejlődést mutatott mindennemű hormonális és vizuális eltérés nélkül. Esetbemutatásunk megerősíti, hogy a septum pellucidum izolált hiánya önmagában lehet egy tünetmentes anatómiai variáció, melynek praenatalis diagnosztikai algoritmusában a vizuális traktus és az agyszerkezet pontosabb megítélése kapcsán a magas mágneses térerővel végzett magzati MR-vizsgálat kulcsfontosságú szerepet játszik, és lehetőséget biztosíthat a septoopticus dysplasia praenatalis kizárására. Orv Hetil. 2020; 161(52): 2195–2200. Summary. Septo-optic dysplasia is characterized as a midline anomaly with agenesis of the septum pellucidum, optic nerve hypoplasia and pituitary dysfunction. The septal agenesis can occur in isolated form, but its prenatal differentiation from septo-optic dysplasia can be challenging. The isolated agenesis of septum pellucidum is an asymptomatic anatomical variation, based on the few literature data available. We report a case where prenatally performed high magnetic field magnetic resonance imaging helped the differential diagnosis by visualizing and assessing thickness of the optic nerves and chiasma. The development of the infant was followed for 24 months and showed no abnormalities. Our case report confirms that isolated agenesis of the septum pellucidum is probably an asymptomatic variation and the visualization of the optic nerves with high magnetic field fetal MRI could be a crucial point of the differential diagnosis and provide possibility to exclude septo-optic dysplasia in utero. Orv Hetil. 2020; 161(52): 2195–2200.
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Smal, J., J. Closset, G. Hennen et P. de Meyts. « Receptor-binding and down-regulatory properties of 22000-Mr human growth hormone and its natural 20000-Mr variant on IM-9 human lymphocytes ». Biochemical Journal 225, no 2 (15 janvier 1985) : 283–89. http://dx.doi.org/10.1042/bj2250283.
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Our earlier binding studies of the 22000- and 20000-Mr variants of human growth hormone (somatotropin) to pregnant-rabbit liver and mammary receptors [Closset, Smal, Gomez & Hennen (1983) Biochem. J. 214, 885-892] suggested that the 20000-Mr variant was a lower-affinity analogue of the 22000-Mr molecule. Since the receptor population in these tissues is not fully characterized, we have now investigated the binding of both variants to the well-characterized and highly specific human-growth-hormone receptor of the human lymphocyte IM-9 cell line. The maximum bindability of radioiodinated 22000- and 22000-Mr to IM-9 cells was 60 and 45% respectively. Both hormone variants have essentially the same binding characteristics: slow association (equilibrium reached in 8-10h at 30 degrees C), poor reversibility (‘tight binding’), linear Scatchard plot, same specificity as shown by lack of competition by bovine, porcine or equine growth hormones or human growth hormone-(32-46)-(missing in the 20000-Mr variant),-(1-134)- and -(141-191)-peptides. Both unlabelled hormones inhibit binding of both tracers completely, with the 20000-Mr variant being only half as potent as the 22000-Mr one. The apparent affinity is 2.8 × 10(9)M-1 for the 22000-Mr variant and 1.6 × 10(9)M-1 for the 20000-Mr variant. This decreased affinity of the 20000-Mr variant appears to be due to a lower association rate constant. Concentrations (5 ng/ml) of the two variants that occupy about 15% of the total sites induce a marked down-regulation of the receptors after 18h incubation, but the 20000-Mr variant (50% decrease) has a smaller effect than the 22000-Mr variant (75% decrease). Thus the only consequence of the residues-32-46 deletion in the 20000-Mr variant is a lower association rate and affinity for the IM-9 lymphocyte human-growth-hormone receptor. The close binding characteristics of the two forms suggest that the known differences in their insulin-like effects cannot be explained by differences in the nature of their interaction with the human-growth-hormone receptor.
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Gerçek, Muhammed, Anca A. Irimie, Mustafa Gerçek, Henrik Fox, Vera Fortmeier, Tanja K. Rudolph, Volker Rudolph et Kai P. Friedrichs. « Dynamics of Cognitive Function in Patients with Heart Failure Following Transcatheter Mitral Valve Repair ». Journal of Clinical Medicine 11, no 14 (9 juillet 2022) : 3990. http://dx.doi.org/10.3390/jcm11143990.
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Aims: Interventional transcatheter edge-to-edge mitral valve repair (TMVR) is an established treatment option for patients with severe mitral regurgitation (MR) and high operative risk. Cognitive impairment is one of the most common conditions among often extensive comorbidities in these patients. The specific patterns of cognitive decline and particularly the effect of TMVR are not well described. Thus, this study aimed to investigate into the impact of TMVR on cognitive impairment, exercise capacity, and quality of life. Methods: Cognitive function (executive, naming, memory, attention, language, abstraction, and orientation) was assessed with the standardized Montreal Cognitive Assessment test (MoCA; range between 0 and 30 points) before and 3 months after TMVR in 72 consecutive patients alongside echocardiographic examination and assessment of exercise capacity (six-minute walk test) as well as quality-of-life questionnaires (Minnesota living with heart failure questionnaire, MLHF-Q). Results: Patients’ median age was 81 [76.0; 84.5] years, 39.7% were female with a median EuroScore II of 4.4% [2.9; 7.7]. The assessment of cognitive function showed a significant improvement of the cumulative MoCA-Test result (from 22.0 [19.0; 24.5] to 24 [22.0; 26.0]; p < 0.001) with significant changes in the subcategories executive (p < 0.001), attention (p < 0.001), abstraction (p < 0.001), and memory (p < 0.001). In addition, quality of life (from 47.5 [25.0; 69.3] to 24.0 [12.0; 40.0]; p < 0.001) and exercise capacity (from 220.0 m [160.0; 320.0] to 280.0 m [200.0; 380.0]; p = 0.003) increased significantly 3 months after the TMVR procedure. Conclusions: TMVR leads to a significant improvement of cognitive function, exercise capacity, and quality of life in patients with chronic heart failure in 3 months follow up and again highlights the benefit of the evermore established TMVR procedure for patients with high operative risk.
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Manjón, José V., Pierrick Coupé, Luis Martí-Bonmatí, D. Louis Collins et Montserrat Robles. « Adaptive non-local means denoising of MR images with spatially varying noise levels ». Journal of Magnetic Resonance Imaging 31, no 1 (20 décembre 2009) : 192–203. http://dx.doi.org/10.1002/jmri.22003.
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Lessa, Cleber Rodrigo de Lima, Douglas Martinazzi, Arlan Pacheco Figueiredo, Rodrigo Batista Machado, Claudia Fanezi et Telmo Strohaecker. « Microstructural behavior of SAF 2205 Duplex Stainless Steel Welded by Friction Hydro Pillar Processing ». Materials Research 19, no 4 (18 juillet 2016) : 928–36. http://dx.doi.org/10.1590/1980-5373-mr-2016-0023.
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Biko, David M., Richard Davidson, Andres Pena et Diego Jaramillo. « Proximal focal femoral deficiency : evaluation by MR imaging ». Pediatric Radiology 42, no 1 (10 septembre 2011) : 50–56. http://dx.doi.org/10.1007/s00247-011-2203-3.
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Cho, Zang-Hee, Chang-Ki Kang, Chan-A. Park, Suk-Min Hong, Sang-Hoon Kim, Seung-Taek Oh et Young-Bo Kim. « Microvascular functional MR angiography with ultra-high-field 7 t MRI : Comparison with BOLD fMRI ». International Journal of Imaging Systems and Technology 22, no 1 (14 février 2012) : 18–22. http://dx.doi.org/10.1002/ima.22008.
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Ley, Sebastian, Karl-Friedrich Kreitner, Christian Fink, Claus P. Heussel, Mathias M. Borst et Hans-Ulrich Kauczor. « Assessment of pulmonary hypertension by CT and MR imaging ». European Radiology 14, no 3 (1 mars 2004) : 359–68. http://dx.doi.org/10.1007/s00330-003-2208-x.
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Koenig, James Karl, Maya E. Pring et Jerry R. Dwek. « MR evaluation of femoral neck version and tibial torsion ». Pediatric Radiology 42, no 1 (13 août 2011) : 113–15. http://dx.doi.org/10.1007/s00247-011-2206-0.
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Whelihan, Matthew F., et Kenneth G. Mann. « Plasma Procofactor Activation by Factor Xla ». Blood 112, no 11 (16 novembre 2008) : 1024. http://dx.doi.org/10.1182/blood.v112.11.1024.1024.
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Abstract The procofactors FV and FVIII are activated by thrombin, FXa and plasmin. During contact pathway-initiated thrombin generation, FXIa activates FIX thus feeding into the coagulation cascade; however, the procofactors FVIII and FV must be activated to achieve a robust level of thrombin generation. We tested the hypothesis that FXIa can activate FV and FVIII. FV (1uM) was subjected to FXIa (100nM) proteolysis. During the reaction the relative activity and integrity were measured at selected time points using a one stage PT clotting assay and SDS-PAGE. Over the 60 minute time course, FV showed a transient 50% activation followed by a reduction in activity to 20%. SDS-PAGE analyses showed that proteolysis of FV by FXIa initially generated fragments with mobilities similar to those produced by α-thrombin. This activation and inactivation pattern suggested that FXIa makes the required activation cleavages at R709, R1018 and R1545 coincidently with inactivating proteolyses. FV was activated with α-thrombin and the reaction quenched by the addition of hirudin prior to FXIa proteolysis. FVa’s cofactor activity was reduced by 50% after 30 min and 80% after 60 min. Analysis of the FXIa cleavage process by SDS-PAGE under reducing conditions showed no intact heavy chain and significant proteolysis of the light chain after 30 minutes. In addition to the Mr = 105000 (HC) and Mr = 75000 (LC), six new products were identified by SDS-PAGE under reducing conditions: Mr = 54000, 50000, 48000, 30000, 22000 and 20000. NH2-terminal sequence analysis indicated a single cleavage in the light chain at R1765 yielding the products Mr = 50000, 48000: (1766à2196) and the Mr = 30000 (1546à1764), also seen with plasmin and FXa. A cleavage in the heavy chain represented by the Mr = 22000, 20000 (R511à709) fragments is also observed. Sequence analysis determined that the Mr = 54000 fragment represented the NH2-terminus of the heavy chain. Western analysis using a heavy chain antibody showed a transient band Mr = 75000 lying under the light chain that is consistent with an initial cleavage R510. A subsequent cleavage, which is coincident with a decrease in the cofactor’s activity, results in a Mr = 30000 product which is consistent with a cleavage somewhere COOH-terminal to R306(R316?). Activity analyses suggest that the initial cleavage in the heavy chain at R510 leads to a FVaXla 1 molecule with similar activity (50%) to that seen in FVa cleaved by APC in the absence of phospholipid. The FVaXla 1 was treated with APC resulting in complete inactivation of the cofactor. We have also observed an analogous FXIa cleavage pattern in FVIII; however sequencing analysis has not yet been attempted. These data suggest that factor XIa may play a role in procofactor activation and inactivation of FV and FVIII in the context of contact pathway-initiated blood coagulation. Figure Figure
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Lee, Chan Woo, In-Ho Kim et Hyung-Jo Jung. « Fabrication and Characterization of Natural Rubber-Based Magnetorheological Elastomers at Large Strain for Base Isolators ». Shock and Vibration 2018 (4 juin 2018) : 1–12. http://dx.doi.org/10.1155/2018/7434536.
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To withstand harsh conditions and have a moderate strength, it is desirable to use natural rubber for base isolators. In addition, previous studies have measured the magnetorheological (MR) effect under low-strain range, mostly within 10%. In the reality, it is necessary to evaluate the performance under large-strain range for base isolators. In this study, material properties of natural rubber-based MREs with various mixing ratios were evaluated under large-strain range (~100%). In the first step, MREs with various iron ratios were fabricated and evaluated to observe the MR effect according to the ratio and arrangement of iron powder. As a result, the highest MR effect (22.0% at 100% strain) and damping ratio (10.29%) were observed in the sample with 35% iron ratio, and the MR effect of the isotropic and the anisotropic MRE did not show significant difference under large-strain (50~100%). In the second step, MRE samples containing the optimum iron ratio (investigated in the first step) and various mixing ratios of carbon black and naphthenic oil were prepared. As a result, the MRE containing 60phr of carbon black and 40phr of naphthenic oil had the highest MR effect (33.8% at 100% strain). Compared to the case without additives, it showed an obvious improvement.
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Zhang, Jun, Xiao Ling Yu, Lei Xu, Fang Zhi Li et Yong Gang Li. « Sequence Characterization of matrix protein (M1) in influenza A viruses (H1, H3 and H5) ». Microbiology Research 2, no 1 (7 octobre 2011) : 16. http://dx.doi.org/10.4081/mr.2011.e16.
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<p><strong> </strong>This study brings the analysis of amino acid sequences of matrix protein (M1) from the influenza virus A (H1N1, H3N2 and H5N1) during 2007-2208. 741 sequences of M1 were compared, of them, H1N1 388; H3N2 251 and H5N1 102. Even though, the M1 is relatively conserved among the influenza A viruses, we found some variations in the M1 among the viruses, H1N1, H3N2 and H5N1. The nuclear localization signal at amino acid 101 to 105 is RKLKR for H1N1 and H3N2, but for H5N1 is KKLKR. All differences of amino acid in M1 of H1, H3 and H5 were listed. 80 sequences of M1 of H1N1 H3N2 and H5N1 were used for phylogenetic analysis. There is no reasontantment found in the M1 among these subtypes. Further study is needed to study the differences of the function of M1 among H1N1, H3N2 and H5N1. The M1 of H5N1 may contribute to the high pathogenesis to this virus.</p>
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Boldt, Julian, Kurt Rottner, Marc Schmitter, Andreas Hopfgartner, Peter Jakob, Ernst-Jürgen Richter et Olga Tymofiyeva. « High-resolution MR imaging for dental impressions : a feasibility study ». Clinical Oral Investigations 22, no 3 (19 septembre 2017) : 1209–13. http://dx.doi.org/10.1007/s00784-017-2204-1.
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Kulik, D. K., et A. T. Varakin. « Selenium-containing drug together with the feed additive Benut in the rations of steers ». Kormlenie sel'skohozjajstvennyh zhivotnyh i kormoproizvodstvo (Feeding of agricultural animals and feed production), no 5 (28 avril 2022) : 13–20. http://dx.doi.org/10.33920/sel-05-2205-02.
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Currently, there is great interest in the use of selenium drugs in animal husbandry. Chickpea is high-containing in selenium and protein. The feed additive Benut, made on the basis of chickpea, has a high content of selenium. At the same time, its active interaction with proteins was revealed. The purpose of the work was to increase the meat productivity and quality of beef of steers when using the selenium-containing drug DAFS-25 in rations together with the feed additive Benut. In order to conduct the experiment, according to the principle of analogues 3 groups of Aberdeen-Angus steers were formed at the age of 9 months for 15 heads in each group. The duration of the experiment was 172 days including the main period 150 days. In the main period, the steers of the 1st control group received the main ration (MR), the 2nd experimental group received MR + DAFS-25 (1,6 mg/kg of concentrates) and the 3rd experimental group received MR + 0,5 kg/head/day of the feed additive Benut (instead of an equivalent amount of concentrates) + DAFS-25 to ensure the content of selenium as in the ration of animals of the 2nd experimental group. The beef productivity of fattened steers of Aberdeen-Angus breed was studied and also indicators of blood composition, digestibility and assimilation of feed nutrients, beef quality and efficiency of its production, when used in rations of the drug DAFS-25 separately and in combination with the feed additive Benut. Profit from the sale of beef in the 2nd experimental group was received by 84,4 rubles more and in the 3rd experimental group by 574,8 rubles more than in the 1st control group. In the 2nd and 3rd experimental groups the profitability level was 1,2 and 13,2 % higher than in the 1st control group (27,3 %).
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Lee, Seyoung, Taegyu Um, Jeeyeon Lee, Peter Haseok Kim, Monica Yadav, Maria J. Chuchuca, Liam Il-Young Chung et Young Kwang Chae. « Abstract 3844 : Clinical implications of mixed response on prognosis of non-small cell lung cancer (NSCLC) patients treated with Immunotherapy ». Cancer Research 84, no 6_Supplement (22 mars 2024) : 3844. http://dx.doi.org/10.1158/1538-7445.am2024-3844.
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Abstract Background: Current methods for assessing the response of lung cancer patients to therapy (e.g. RECIST criteria) lack consideration for mixed response (MR) where some lesions increase while others decrease simultaneously. MR poses a challenge in deciding the continuation of therapy. Understanding the clinical implications of MR on patient prognosis within radiographic response categories is crucial for establishing effective treatment strategies for NSCLC. Methods: This study analyzed 177 NSCLC patients with ≥2 lesions receiving first-line systemic treatment with immunotherapy. Clinical response was evaluated by RECIST v1.1 and immune-related RECIST (irRECIST). MR was defined as the simultaneous presence of ≥1 lesion increase and ≥1 lesion decrease during therapy. Two different definitions of MR were utilized. Definition-A (MR-A): the simultaneous presence of one or more lesions increasing ≥5mm and one or more lesions decreasing ≥5mm during therapy (Δ [baseline - first follow-up] ≥ 5 mm); and Definition-B (MR-B): the simultaneous presence of one or more lesions increasing >1mm and one or more lesions decreasing >1mm during therapy (any Δ [baseline - first follow-up]). Subgroup analysis was conducted using 94 patients with only intrathoracic lesions. Results: Among the 177 patients, tumor responses based on RECIST were 3 CR (1.7%),42 PR (23.7%), 87 SD (49.2%), and 45 PD (25.4%). Based on irRECIST, responses were 3 CR (1.7%), 46 PR (26.0%), 89 SD (50.3%), and 39 PD (22.0%). MR-A and MR-B occurred in 19.8% (n=35) and 45.2% (n=80) of cases, respectively. In the irRECIST PD group, MR-A demonstrated significantly different median progression-free survival (mPFS) and median overall survival (mOS) compared to non-MR-A (p<0.020, p<0.005, respectively). The mPFS for MR-A group was 1.4 months (range 0.5-52.9) and non-MR-A group was 5.5 months (range 0.2-97.2) with the hazard ratio being 2.91 (95% CI 1.13-7.51). The mOS for MR-A and non-MR-A groups were 4.8 months (range 0.7-61.5) and 11.8 months (range 0.2-97.2), respectively, hazard ratio 4.87 (95% CI 1.43-16.56). No other significant results were found for other RECIST and irRECIST categories. Subgroup analysis of only intrathoracic lesion patients revealed no statistically significant results. Conclusion: Contrary to our hypothesis, MR did not modify prognosis within the RECIST or irRECIST category. MR-A or MR-B in the RECIST or irRECIST PD group did not show a better prognosis, indicating the complexity of mixed responses in NSCLC patients treated with immunotherapy. Further research with larger cohorts are warranted. Citation Format: Seyoung Lee, Taegyu Um, Jeeyeon Lee, Peter Haseok Kim, Monica Yadav, Maria J. Chuchuca, Liam Il-Young Chung, Young Kwang Chae. Clinical implications of mixed response on prognosis of non-small cell lung cancer (NSCLC) patients treated with Immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3844.
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Choi, Seung Hong, Keon Ha Kim, Woo Kyung Moon, Hyo-Cheol Kim, Joo Hee Cha, Jin Ho Paik et Kee-Hyun Chang. « Comparison of lymph node metastases assessment With the use of USPIO-enhanced MR imaging at 1.5 T versus 3.0 T in a rabbit model ». Journal of Magnetic Resonance Imaging 31, no 1 (20 décembre 2009) : 134–41. http://dx.doi.org/10.1002/jmri.22020.
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Barnard, Trish. « Indigenised Souvenirs and Homewares in the Glenn Cooke Collection ». Memoirs of the Queensland Museum - Culture 10 (décembre 2016) : 107–15. http://dx.doi.org/10.17082/j.2205-3239.10.2016-08.
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This paper offers an interpretive evaluation of a collection that was donated to the Queensland Museum by Mr Glenn R. Cooke. The collection consists of 1,395 souvenir tourist objects and items of domestic homeware decorated with indigenised motifs that were manufactured for the Australian market between the 1930s and the 1980s. The motifs on many of the objects are based on traditional designs of rainforest Aboriginal groups from the Wet Tropics of North Queensland, misappropriated by non-Indigenous artists and craft-workers. Research into the sources of the motifs traces the transformation of the original designs into decorative patterns for domestic homeware and tourist products.
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Komachali, Sajad Rafiee, Zakieh Siahpoosh et Mansoor Salehi. « Two novel mutations in ALDH18A1 and SPG11 gene found by whole-exome sequencing in spastic paraplegia disease patients in Iran ». Genomics & ; Informatics 20, no 3 (30 septembre 2022) : e30. http://dx.doi.org/10.5808/gi.22030.
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Hereditary spastic paraplegia is a not common inherited neurological disorder with heterogeneous clinical expressions. ALDH18A1 (located on 10q24.1) gene-related spastic paraplegias (SPG9A and SPG9B) are rare metabolic disorders caused by dominant and recessive mutations that have been found recently. Autosomal recessive hereditary spastic paraplegia is a common and clinical type of familial spastic paraplegia linked to the SPG11 locus (locates on 15q21.1). There are different symptoms of spastic paraplegia, such as muscle atrophy, moderate MR, short stature, balance problem, and lower limb weakness. Our first proband involves a 45 years old man and our second proband involves a 20 years old woman both are affected by spastic paraplegia disease. Genomic DNA was extracted from the peripheral blood of the patients, their parents, and their siblings using a filter-based methodology and quantified and used for molecular analysis and sequencing. Sequencing libraries were generated using Agilent SureSelect Human All ExonV7 kit, and the qualified libraries are fed into NovaSeq 6000 Illumina sequencers. Sanger sequencing was performed by an ABI prism 3730 sequencer. Here, for the first time, we report two cases, the first one which contains likely pathogenic NM_002860: c.475C>T: p.R159X mutation of the ALDH18A1 and the second one has likely pathogenic NM_001160227.2: c.5454dupA: p.Glu1819Argfs Ter11 mutation of the SPG11 gene and also was identified by the whole-exome sequencing and confirmed by Sanger sequencing. Our aim with this study was to confirm that these two novel variants are direct causes of spastic paraplegia.
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Molnarova, Zuzana, Marie Machatkova, Ladislav Machal, Jindra Horakova et Katerina Hanzalova. « A potential relationship between the acrosome response characteristics of bovine spermatozoa and their in vitro fertilizing ability ». Zygote 14, no 1 (février 2006) : 63–69. http://dx.doi.org/10.1017/s096719940600356x.
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The aim of the work was to study a potential relationship between acrosome response characteristics of bovine spermatozoa and their ability to fertilize oocytes and produce in vitro embryos. Sperm of artificial insemination bulls with a high rate (22.0 ± 4.1%, group A, n = 7) or a low rate (10.3 ± 4.1%, group B, n = 8) of embryos were used. For acrosome assessment, motile spermatozoa from a Percoll gradient were incubated with or without heparin and examined by the fix-vital sperm assay (FVSA). The differences between the heparin-treated (H+) and the non-treated (H−) spermatozoa were significant (p < 0.01) in all bulls at all tested intervals. According to the kinetics of the heparin response, the bulls fell into three categories: fast (FR, n = 7), moderate (MR, n = 5) or slow (SR, n = 3) acrosome responses (p < 0.01). Five MR bulls were found in group A in comparison with two MR bulls in group B (57.1 vs 12.5%; p < 0.05). Intensity of the acrosome response (response index) was significantly higher in bull group A compared with bull group B (7.0 vs 4.6, p < 0.01). A positive correlation was recorded between response index and embryo rate (r = 0.668, p < 0.01). In conclusion (a) the kinetics of spermatozoa response to heparin may be important for in vitro fertilization, bulls with a moderate response appearing to be most suitable for embryo production; (b) greater spermatozoa response to heparin was related to more effective embryo production.
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Liu, Xing-Hai, Jian-Quan Weng et Cheng-Xia Tan. « Synthesis, Crystal Structure, and Fungicidal Activity of 5-(4-cyclopropyl-5-((3-fluorobenzyl)thio)-4H-1,2,4-triazol-3-yl)-4-methyl-1,2,3-thiadiazole ». Journal of Chemistry 2013 (2013) : 1–5. http://dx.doi.org/10.1155/2013/306361.
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A new 1,2,3-thiadiazole compound was synthesized and characterized. The crystal structure of the title compound (C15H14FN5S2, Mr = 347.43) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P-1 witha=7.0490(14),b=9.0212(18),c=12.799(3) Å,α= 89.97(3)°,β= 82.27(3)°,γ= 73.17(3)°,V= 771.3(3) Å3, Z = 2, F(000) = 360, Dc = 1.496 g/cm3,μ= 0.036 mm−1, the finalR1= 0.0358, andwR2= 0.0986 for 2204 observed reflections withI>2σ(I). A total of 5697 reflections were collected, of which 2719 were independent (Rint=0.0028). The herbicidal activity of title compound was determined; the results showed that the title compound displayed excellent fungicidal activity.
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Gaudino, Chiara, Raluca Cosgarea, Sabine Heiland, Réka Csernus, Bruno Beomonte Zobel, Mirko Pham, Ti-Sun Kim, Martin Bendszus et Stefan Rohde. « MR-Imaging of teeth and periodontal apparatus : an experimental study comparing high-resolution MRI with MDCT and CBCT ». European Radiology 21, no 12 (31 juillet 2011) : 2575–83. http://dx.doi.org/10.1007/s00330-011-2209-0.
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Yuan, Z. J., R. Zhao, J. Y. Li, M. K. Yao, S. Y. Liu Yue, S. X. Zhang, X. Li et C. Wang. « AB0052 GENETIC EVIDENCE REVEALS CAUSAL LINK BETWEEN RHEUMATOID ARTHRITIS AND mTOR PROTEINS： A MENDELIAN RANDOMIZATION STUDY ». Annals of the Rheumatic Diseases 82, Suppl 1 (30 mai 2023) : 1205.1–1205. http://dx.doi.org/10.1136/annrheumdis-2023-eular.3751.
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BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease with hyperplasia of joint tissue and synovial inflammation1. And the mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase, which relates with cellular metabolism, promotes cell growth and inflammatory process2. Some studies show that some downstream proteins of mTOR are associated with RA, but having no directly genetic evidence.ObjectivesWe conducted Mendelian randomization (MR) study to discover the genetically and statistically casual association between mTOR and RA.MethodsA two-sample MR study was applied to investigate the association. Firstly, the GWAS data of 14 downstream proteins of mTOR, including plasma RP-S6K, EIF-4EBP2 and so on was obtain from the 3,301 European samples. And a summary statistic involved 14,361 cases and 43,923 controls was also acquired from the IEU OpenGWAS database. Meanwhile, we extracted Single-nucleotide polymorphisms (SNPs) which were related with mTOR (P < 1.0×10-5) and satisfied the three assumptions for MR analysis as instrumental variables (IVs). Then, Inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression were performed for MR statistical analysis by R Studio with packages “TwoSampleMR”. Additionally, MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis was conducted to detect outlier instrument and remove pleiotropy. A leave-one-out analysis was conducted to avoid bias caused by a single SNP.ResultsOur study showed that no indication supporting the fact that the 14 downstream proteins of mTOR were causally associated with RA risk. The 15 SNPs of RP-S6K, 12 SNPs of EIF-4EBP2 and so on were selected as IVs for each 14 proteins. MR results showed that there was no causal relationship between RP-S6K and RA (OR = 1.03, CI: 0.89 - 1.20, P = 0.68). The results were same for EIF-4EBP2 (OR = 0.89, CI: 0.74 - 1.06, P = 0.18) and the other 12 proteins. No single SNP significantly biased the causal effect of mTOR and RA. No significant directional horizontal pleiotropy between each 14 downstream proteins and RA was presented.ConclusionOur study showed that a cause–effect connection did not appear to exist between mTOR proteins and RA, the findings of this study increased our understanding of the genetic associations, and may provide novel insights into the functional mechanism underlying the associations between SNPs and mTOR and RA.References[1]McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis.The New England journal of medicine2011;365(23):2205-19. doi: 10.1056/NEJMra1004965 [published Online First: 2011/12/14][2]Li PP, Liu DD, Liu YJ, et al. BAFF/BAFF-R involved in antibodies production of rats with collagen-induced arthritis via PI3K-Akt-mTOR signaling and the regulation of paeoniflorin.Journal of ethnopharmacology2012;141(1):290-300. doi: 10.1016/j.jep.2012.02.034 [published Online First: 2012/03/07]Acknowledgements:NIL.Disclosure of InterestsNone Declared.
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Vasquez, R. J., D. L. Gard et L. Cassimeris. « XMAP from Xenopus eggs promotes rapid plus end assembly of microtubules and rapid microtubule polymer turnover. » Journal of Cell Biology 127, no 4 (15 novembre 1994) : 985–93. http://dx.doi.org/10.1083/jcb.127.4.985.
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We have used video-enhanced DIC microscopy to examine the effects of XMAP, a Mr 215,000 microtubule-associated protein from Xenopus eggs (Gard, D.L., and M. W. Kirschner. 1987. J. Cell Biol. 105:2203-2215), on the dynamic instability of microtubules nucleated from axoneme fragments in vitro. Our results indicate that XMAP substantially alters the parameters of microtubule assembly at plus ends. Specifically, addition of 0.2 microM XMAP resulted in (a) 7-10-fold increase in elongation velocity, (b) approximately threefold increase in shortening velocity, and (c) near elimination of rescue (the switch from rapid shortening to elongation). Thus, addition of XMAP resulted in the assembly of longer, but more dynamic, microtubules from the plus ends of axonemes which upon catastrophe disassembled back to the axoneme nucleation site. In agreement with previous observations (Gard, D.L., and M. W. Kirschner. 1987. J. Cell Biol. 105:2203-2215), the effects of XMAP on the minus end were much less dramatic, with only a 1.5-3-fold increase in elongation velocity. These results indicate that XMAP, unlike brain MAPs, promotes both polymer assembly and turnover, and suggests that the interaction of XMAP with tubulin and the function of XMAP in vivo may differ from previously characterized MAPs.
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Kollmer, Jennifer, Markus Weiler, Jan Purrucker, Sabine Heiland, Stefan O. Schönland, Ernst Hund, Christoph Kimmich et al. « MR neurography biomarkers to characterize peripheral neuropathy in AL amyloidosis ». Neurology 91, no 7 (20 juillet 2018) : e625-e634. http://dx.doi.org/10.1212/wnl.0000000000006002.
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ObjectiveTo detect, localize, and quantify peripheral nerve lesions in amyloid light chain (AL) amyloidosis by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings.MethodsWe prospectively examined 20 patients with AL-polyneuropathy (PNP) and 25 age- and sex-matched healthy volunteers. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into mild and moderate PNP. MRN in a 3.0 tesla scanner with anatomical coverage from the lumbosacral plexus and proximal thigh down to the tibiotalar joint was performed by using T2-weighted and dual-echo 2-dimensional sequences with spectral fat saturation and a 3-dimensional, T2-weighted inversion recovery sequence. Besides evaluation of nerve T2-weighted signal, detailed quantification of nerve injury by morphometric (nerve caliber) and microstructural MRN markers (proton spin density, T2 relaxation time) was conducted.ResultsNerve T2-weighted signal increase correlated with disease severity: moderate (420.2 ± 60.1) vs mild AL-PNP (307.2 ± 17.9; p = 0.0003) vs controls (207.0 ± 6.4; p < 0.0001). Proton spin density was also higher in moderate (tibial: 525.5 ± 53.0; peroneal: 553.6 ± 64.5; sural: 492.0 ± 56.6) and mild AL-PNP (tibial: 431.6 ± 22.0; peroneal: 457.6 ± 21.7; sural: 404.8 ± 25.2) vs controls (tibial: 310.5 ± 14.1; peroneal: 313.6 ± 11.6; sural: 261.7 ± 11.0; p < 0.0001 for all nerves). T2 relaxation time was elevated in moderate AL-PNP only (tibial: p = 0.0106; peroneal: p = 0.0070; sural: p = 0.0190). Tibial nerve caliber was higher in moderate (58.0 ± 8.8 mm3) vs mild AL-PNP (46.5 ± 2.5 mm3; p = 0.008) vs controls (39.1 ± 1.2 mm3; p < 0.0001).ConclusionsMRN detects and quantifies peripheral nerve injury in AL-PNP in vivo with high sensitivity and in close correlation with the clinical stage. Quantitative parameters are feasible new imaging biomarkers for the detection of early AL-PNP and might help to monitor microstructural nerve tissue changes under treatment.
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deVries, A., W. Judmaier, J. Griebel, Ch Kremser, T. Gneiting, S. Peer, F. Aichner et P. Lukas. « 2206 Monitoring of tumor microcirculation during fractionated radiotherapy in patients with rectal carcinomas : A clinical study using contrast enhanced MR imaging ». International Journal of Radiation Oncology*Biology*Physics 36, no 1 (janvier 1996) : 377. http://dx.doi.org/10.1016/s0360-3016(97)85777-x.
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Wawolangi, Natalia Enjellina, Grace Adonia Josephine Rumagit et Charles Reijnaldo Ngangi. « Profil Usaha Mie Ba Garuda Asli Di Maumbi Kecamatan Kalawat Kabupaten Minahasa Utara ». Journal of Agribusiness and Rural Development (Jurnal Agribisnis dan Pengembangan Pedesaan) 5, no 4 (8 juillet 2024) : 1–8. http://dx.doi.org/10.35791/agrirud.v5i4.56409.
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The purpose of this research is to describe the Business Profile of Mie Ba Garuda Original Maumbi, Kalawat District, North Minahasa Regency. Identify the history contained in the Mie Ba Garuda Asli restaurant. Identify what raw materials are used in the process of making Original Ba Garuda Noodles. Analyzing the profit of selling the number of ba meat noodle products produced by Mie Ba Garuda Asli. The results showed that the original ba garuda noodle business was opened in 1965 by Mr. Endi Lucas and was located on Jalan Garuda. This Mie Ba Garuda Asli restaurant is open every Monday - Saturday from 08.00 - 22.00. The amount of noodle raw materials used ranges from 257-260 kg and the pork used ranges from 58-60 kg per month. Every day is the highest demand and at the highest demand, the profit earned is IDR 36,960,000 per month.
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QIN, Yong-Mei, Matti H. POUTANEN, Heli M. HELANDER, Ari-Pekka KVIST, Kirsi M. SIIVARI, Werner SCHMITZ, Ernst CONZELMANN, Ulf HELLMAN et J. Kalervo HILTUNEN. « Peroxisomal multifunctional enzyme of β-oxidation metabolizing d-3-hydroxyacyl-CoA esters in rat liver : molecular cloning, expression and characterization ». Biochemical Journal 321, no 1 (1 janvier 1997) : 21–28. http://dx.doi.org/10.1042/bj3210021.
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In the present study we have cloned and characterized a novel rat peroxisomal multifunctional enzyme (MFE) named perMFE-II. The purified 2-enoyl-CoA hydratase 2 with an Mr of 31500 from rat liver [Malila, Siivari, Mäkelä, Jalonen, Latipää, Kunau and Hiltunen (1993) J. Biol. Chem. 268, 21578–21585] was subjected to tryptic fragmentation and the resulting peptides were isolated and sequenced. Surprisingly, the full-length cDNA, amplified by PCR, had an open reading frame of 2205 bp encoding a polypeptide with a predicted Mr of 79331 and contained a potential peroxisomal targeting signal in the C-terminus (Ala-Lys-Leu). The sequenced peptide fragments of hydratase 2 gave a full match in the middle portion of the cDNA-derived amino acid sequence. The predicted amino acid sequence showed a high degree of similarity with pig 17β-hydroxysteroid dehydrogenase type IV and MFE of yeast peroxisomal β-oxidation. Recombinant perMFE-II (produced in Pichia pastoris) had 2-enoyl-CoA hydratase 2 and d-specific 3-hydroxyacyl-CoA dehydrogenase activities and was catalytically active with several straight-chain trans-2-enoyl-CoA, 2-methyltetradecenoyl-CoA and pristenoyl-CoA esters. The results showed that in addition to an earlier described multifunctional isomerase–hydratase–dehydrogenase enzyme from rat liver peroxisomes (perMFE-I), another MFE exists in rat liver peroxisomes. They both catalyse sequential hydratase and dehydrogenase reactions of β-oxidation but through reciprocal stereochemical courses.
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Baricos, W. H., Y. Zhou, R. W. Mason et A. J. Barrett. « Human kidney cathepsins B and L. Characterization and potential role in degradation of glomerular basement membrane ». Biochemical Journal 252, no 1 (15 mai 1988) : 301–4. http://dx.doi.org/10.1042/bj2520301.
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Cathepsins B and L were purified from human kidney. SDS/polyacrylamide-gel electrophoresis demonstrated that cathepsins B and L, Mr 27000-30000, consist of disulphide-linked dimers, subunit Mr values 22000-25000 and 5000-7000. The pH optimum for the hydrolysis of methylcoumarylamide (-NHMec) substrates (see below) is approx. 6.0 for each enzyme. Km and kcat. are 252 microM and 364s-1 and 2.2 microM and 25.8 s-1 for the hydrolysis of Z-Phe-Arg-NHMec (where Z- represents benzyloxycarbonyl-) by cathepsins B and L respectively, and 184 microM and 158 s-1 for the hydrolysis of Z-Arg-Arg-NHMec by cathepsin B. A 10 min preincubation of cathepsin B (40 degrees C) or cathepsin L (30 degrees C) with E-64 (2.5 microM) results in complete inhibition. Under identical conditions Z-Phe-Phe-CHN2 (0.56 microM) completely inhibits cathepsin L but has little effect on cathepsin B. Incubation of glomerular basement membrane (GBM) with purified human kidney cathepsin L resulted in dose-dependent (10-40 nM) GBM degradation. In contrast, little degradation of GBM (less than 4.0%) was observed with cathepsin B. The pH optimum for GBM degradation by cathepsin L was 3.5. Cathepsin L was significantly more active in degrading GBM than was pancreatic elastase, trypsin or bacterial collagenase. These data suggest that cathepsin L may participate in the lysosomal degradation of GBM associated with normal GBM turnover in vivo.
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Ezziddin, Samer, Mared Attassi, Charlotte Jane Yong-Hing, Amir Sabet, Hojjat Ahmadzadehfar, Winfried Willinek, Frank Gruenwald, Stefan Guhlke et Hans-Juergen Biersack. « Factors predicting outcome of G1/2 GEP NET after PRRT with Lu177-octreotate. » Journal of Clinical Oncology 30, no 15_suppl (20 mai 2012) : e14565-e14565. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.e14565.
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e14565 Background: Outcome analyses of G1/2 NEN stage IV after peptide receptor radionuclide therapy (PRRT) are still limited, especially with regard to the impact of the Ki-67 index. This study aims to establish predictors of survival. Methods: Retrospective analysis of 74 consecutive GEP NET patients undergoing PRRT with 177Lu-octreotate. Patients had unresectable metastatic disease and a G1/2 grading (33 pancreatic, 41 non-pancreatic GEP- NET), documented morphologic or clinical progression within < 12 months and/or uncontrolled disease. Response (modified SWOG criteria) was correlated with potential impact factors: origin, function, burden, and uptake of tumor, age, Ki-67-index, Karnofsky score, baseline tumor marker levels. Predictors for survival were analyzed with Kaplan-Meier curves (log-rank test) and multivariate analysis (p<0.05). Results: The response rates were 36.5% PR, 17.6% MR, 35.1% SD, and 10.8% PD for the entire cohort, 54.5% PR, 18.2% MR, 18.2% SD, and 9.1% PD for pancreatic NET, and 22.0% PR, 17.1% MR, 48.8% SD, and 12.2% PD for non-pancreatic GEP-NET. The median progression-free (PFS) and overall (OS) survival was 26 months (95% CI, 18.3 - 33.7) and 55 months (95% CI, 48.8–61.2), respectively. The only factor associated with decreased PFS was a Ki-67 index >10% (p=0.002). For OS, besides the Ki-67 index, a Karnofsky score ≤70% and a baseline NSE of >15 ng/ml independently predicted shorter survival (each p<0.005, HR 3.0 - 3.4). Patients with a Ki-67 index >10% still had a median PFS and OS of 19 and 34 months, respectively. Conclusions: This study confirms the favorable outcome of G1/2 NET after PRRT. Independent predictors of survival are the Ki-67 index, the patient‘s performance status and the baseline NSE level. Nevertheless, patients with a Ki-67 >10% may still benefit from PRRT as demonstrated by the long-term outcome.
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Castillo, C. J., P. Colburn et V. Buonassisi. « Characterization and N-terminal sequence of a heparan sulphate proteoglycan synthesized by endothelial cells in culture ». Biochemical Journal 247, no 3 (1 novembre 1987) : 687–93. http://dx.doi.org/10.1042/bj2470687.
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We have isolated from the conditioned medium of an established endothelial cell line a heparan sulphate proteoglycan whose involvement in the inhibition of the extrinsic coagulation pathway was reported in previous studies [Colburn & Buonassisi (1982) Biochem. Biophys. Res. Commun. 104, 220-227]. The proteoglycan was purified by gel filtration and ion-exchange chromatography, and appears to be free of contaminating proteins as determined by polyacrylamide-gel electrophoresis of the radioiodinated protein core before and after removal of the glycosaminoglycan chains by treatment with heparitinase. By this procedure the Mr of the protein core was estimated to be 22000. The N-terminal end was sequenced up to amino acid 25. The 21st residue is likely to be glycosylated. Analysis of the purified proteoglycan by gel-filtration chromatography yielded Kd values of 0.2 for the whole molecule and 0.35 for the glycosaminoglycan chains. The structure that emerges from these data is that of a heparan sulphate proteoglycan characterized by a relatively small protein core and few glycosaminoglycan chains.
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Landheer, Karl, et Christoph Juchem. « Erratum to : Dephasing optimization through coherence order pathway selection (DOTCOPS) for improved crusher schemes in MR spectroscopy (Magn Reson Med. 2019;81:2209‐2222) ». Magnetic Resonance in Medicine 82, no 2 (2 mai 2019) : 854–55. http://dx.doi.org/10.1002/mrm.27776.
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Autry, Adam, Brian Chung, Hsin-Yu Chen, Jeremy Gordon, Marisa Lafontaine, Susan Chang, Javier Villanueva-Meyer, Peder Larson, Daniel Vigneron et Yan Li. « CBMT-36. INITIAL EXPERIENCE WITH HYPERPOLARIZED [2-13C]PYRUVATE MR IMAGING IN PATIENTS WITH IDH-MUTANT GLIOMA ». Neuro-Oncology 21, Supplement_6 (novembre 2019) : vi41. http://dx.doi.org/10.1093/neuonc/noz175.158.
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Abstract INTRODUCTION Hyperpolarized (HP) carbon-13 MR imaging allows for real-time non-invasive measurement of metabolism. Using HP [2-13C]pyruvate as a molecular probe enables the measurement of both aerobic glycolysis ([2-13C]lactate) and oxidative metabolism (such as [5-13C]glutamate and [5-13C]glutamine). This study presents the initial patient experience of acquiring HP [2-13C]pyruvate MR spectroscopic data. METHODS Two patients who presented with IDH-mutant gliomas (43 year-old male, grade II astrocytoma, RT/TMZ; 33 year-old female, grade III oligodendroglioma, no RT/TMZ) considered radiologically stable post resection were imaged using a 2D chemical shift imaging (CSI) sequence (15.6–18.8cm3 spatial resolution, 20s acquisition), following injection of 0.43mL/kg of 250mM HP [2-13C]pyruvate. HP [2-13C]pyruvate, [5-13C]glutamate, [5-13C]glutamine, and [2-13C]lactate resonances were quantified within a lesion voxel and contralateral normal-appearing voxel. The proton images were aligned to HP data enabled quantification of apparent diffusion coefficients (ADC), perfusion peak height (PH), and MR spectroscopy choline-to-N-acetyl-aspartate indices (CNI). ADC (nADC) and PH (nPH) values were normalized by the median value in normal-appearing white matter. RESULTS Proton exams revealed no Gd-enhancement lesions. For the T2-hyperintense lesion (T2L), volumeT2L=18.4/4.2cc (Patient#1/Patient#2); median ADCT2L =1.86/1.64; max CNIT2L=3.2/6.5; 90th percentile nPHT2L =1.09/2.11. HP data displayed maximum signal-to-noise ratios (SNR) for [2-13C]pyruvate, [5-13C]glutamate, [5-13C]glutamine, and [2-13C]lactate of 1360, 44, 27, and 400, respectively. The HP CSI data contained 15.9/13.7 %T2L; 15.1/4.1 %NAWM; 15.7/22.0 %GM (Patient#1/Patient#2) in selected lesion voxels, while contralateral voxels had %NAWM:%GM of Lesions demonstrated a reduced HP glutamate/pyruvate ratio [#1: 0.0089/0.0102 (lesion/normal voxel); #2: 0.0170/0.0269] and an elevated HP glutamate-to-glutamine ratio in both patients [#1: 0.81/0.66; #2: 0.84/0.66]. DISCUSSION This first patient experience with HP [2-13C]pyruvate showed adequate SNR for quantifying HP [2-13C]pyruvate, [5-13C]glutamate, [5-13C]glutamine, and [2-13C]lactate resonances. Future studies will optimize imaging protocols and expand the patient cohort to evaluate aberrant metabolism related to IDH-mutant tumor.
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Chiang, Anne C., Russell W. Madison, Yanmei Huang, Alexander Fine, Dexter X. Jin, Geoffrey R. Oxnard, Jason Hughes et al. « Abstract 971 : Validation of a tumor-naïve circulating tumor DNA (ctDNA) response monitoring panel in advanced non-small cell lung cancer (aNSCLC) ». Cancer Research 84, no 6_Supplement (22 mars 2024) : 971. http://dx.doi.org/10.1158/1538-7445.am2024-971.
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Abstract Introduction: Monitoring of ctDNA can be a minimally invasive complement to tumor imaging for assessing treatment effect. Technical limitations require methods to distinguish tumor signal from clonal hematopoiesis (CH), often including non-tumor sequencing. We developed a tumor-naïve panel (FoundationOne® Monitor) to quantify ctDNA tumor fraction (TF). TF analytical validation used peripheral blood mononuclear cell (PBMC) sequencing. We then leveraged plasma collected serially from patients with aNSCLC in the real-world (rw) Prospective Clinico-Genomic (PCG; NCT04180176) study to investigate the utility of TF for monitoring therapy (tx) response. Methods: TF was quantified using a combination of aneuploidy and variant allele frequencies of genomic alterations (GAs), while excluding CH mutations and aneuploidy using fragmentomic signal from cfDNA. In the PCG study, data from consenting patients were collected from electronic health records from 23 participating Flatiron Health Research Network sites. We analyzed plasma collected 6-15 weeks after start of tx in exploratory and validation cohorts per prespecified criteria. We defined molecular response (MR) as undetectable TF on tx regardless of baseline TF. Hazard ratios (HR) and 95% confidence Interval (CI) were calculated with univariate Cox proportional hazard regression. Results: For TF validation, 1135 samples separate from the PCG study with paired PBMC results were included. Overall, 24/4274 (0.56%) CH derived non-aneuploidy GAs detected in 1134 samples were falsely classified as somatic. Of these, 4 were detected among 317 samples with no tumor signal, resulting in a false positive TF value (specificity = 98.7%). CH derived aneuploidy was observed in 27 PBMCs and was appropriately filtered during TF estimation in all cases. Assessing the impact of CH aneuploidy filtering on sensitivity, we only identified 1/320 (0.31%) samples where non-CH derived aneuploidy was omitted. To assess clinical validity, 222 patients were analyzed from the PCG study. MR was assessed after a median of 10.8 weeks of tx (IQR 8.9-12.0). In a subset of 152 patients treated with physicians’ choice, MR was associated with favorable rw progression free survival (rwPFS: 9.4 v 2.8 months [mo]; HR = 0.30; 95% CI: [0.21-0.44]) and rw overall survival (rwOS: 22.0 v 7.5 mo; HR = 0.33 [0.22-0.49]). We validated this finding on 70 patients receiving immunotherapy (50 with chemo). Again, MR was associated with favorable rwPFS (9.0 v 2.8 mo; HR = 0.28 [0.16-0.51]) and rwOS (20.2 v 9.4 mo; HR = 0.42 [0.23-0.78]). Conclusions: We describe a highly specific tumor naïve algorithmic filtration of non-tumor signal to enable high confidence ctDNA quantification and MR assessment. On tx MR is associated with favorable outcomes. These findings may enable personalized tx approaches tailored to a patient’s risk of progression and downstream cancer morbidity. Citation Format: Anne C. Chiang, Russell W. Madison, Yanmei Huang, Alexander Fine, Dexter X. Jin, Geoffrey R. Oxnard, Jason Hughes, Zoe June Assaf, Yi Cao, Vladan Antic, Ole Gjoerup, Amanda Young, David Fabrizio, Shaily Lakhanpal, Richard Zuniga, Katja Schulze, Lincoln W. Pasquina. Validation of a tumor-naïve circulating tumor DNA (ctDNA) response monitoring panel in advanced non-small cell lung cancer (aNSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 971.
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SUZUKI, Takashi, Masami NAKANO et Yuichi HIKICHI. « 220 Performance Evaluation of Transfemoral Prostheses Controlled by Optional Motions Using MR Fluid Brake Knee Joint ». Proceedings of Conference of Tohoku Branch 2012.47 (2012) : 246–47. http://dx.doi.org/10.1299/jsmeth.2012.47.246.
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Chen, Wenming, Peng Wei, Shifang Yang, Xiangjun Zheng, Lugui Qiu, Jian Hou, Xuejun Zhang et al. « Transiently Elevated AST/LDH Are Associated with Clinical Response to Recombinant Circularly Permuted TRAIL (CPT) Plus Thalidomide in Patients with Relapsed and/or Refractory Multiple Myeloma ». Blood 124, no 21 (6 décembre 2014) : 3478. http://dx.doi.org/10.1182/blood.v124.21.3478.3478.
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Abstract Introduction: Circularly permuted TRAIL (CPT), a recombinant mutant of human Apo2L/TRAIL, is a promising anti-tumor candidate. In previous phase1/2 clinical trials of single-agent CPT in patients with relapsed and/or refractory multiple myeloma (RRMM), transient elevations of serum AST and LDH were observed early after CPT treatment in most response patients, but not in the non-respondent. Positive correlations were found between increased AST/LDH on day 2 or 3 (24 or 48 hours) after CPT initial dosing and the clinical responses to CPT. Objective: To determine whether transiently elevated AST/LDH is predictive of responses to CPT plus thalidomide in thalidomide-relapsed or refractory MM patient and the time course of AST or LDH elevation. Methods: We retrospectively analyzed the data of a phase 2 study of CPT plus thalidomide. The changes of serum AST, LDH or ALT were analyzed before treatment and on days 2, 3 and 6 after initial dosing. Relationship was evaluated between ΔAST, ΔLDH, ΔALT (ratio of ASTD2, LDHD2 or ALTD2to baseline value) and the best clinical responses. Four MM cell lines (RPMI 8226, NCI-H929, MM.1S, MM.1R) sensitive to CPT were used to detect the concentrations of AST, ALT and LDH in the cytoplasm or the medium of CPT-treated cells, with the purpose of determining whether CPT-induced cell death could result in an elevation of AST or LDH. Results: Of 41 efficacy-evaluable patients, 9(22.0%) achieved a partial response (PR) or better and 14 (34.1%) achieved a minimal response (MR) or better. The serum ASTD2 and LDHD2 levels were dramatically increased from baseline in patients with ≥PR or ≥MR, but not in those with NC/PD. However, serum ALTD2 was comparable to baseline value either in response patients (≥PR or ≥MR) or in non-response ones (NC/PD). Consequently, the median ΔAST or ΔLDH of patients with ≥PR or ≥MR was significantly higher than that of patients with NC/PD (Table 1). The elevation of AST or LDH was transient with a peak on day 2 after treatment, then dramatically declined on day 3, and usually disappeared within one week (at most two weeks for LDH) (Figure 1), which was uniquely observed in the first treatment cycle. A univariate logistic-regression analysis showed that ΔASTwas predictive of achieving responses of ≥MR or not (P=0.04). Indeed, patients with higher level of ΔAST had higher probability of achieving responses of ≥MR (72.7% in patients with ΔAST>1.35 vs. 26.3% in patients with ΔAST≤1.35). In the cytoplasm of MM cell lines, abundant AST and LDH but only detectable level of ALT was observed. There was no significant change in the release rates of AST and LDH with CPT incubation for 1, 2, 3, 4 or 6 hours, even though the cell viabilities at 6h had already declined to about 10-20% of the control cells by ATP chemiluminescent assay. Remarkable increase in the release rates of AST and LDH occurred at 24h, with no evident change of ALT, which was consistent with what was observed in patients in the clinical study. It was suggested that the transient elevation of AST or LDH in RRMM patients was most likely resulted from CPT-induced myeloma cell death. Conclusion: The early transient elevations of serum AST and LDH after CPT plus thalidomide treatment were positively correlated with the clinical responses to CPT plus thalidomide, and were possibly resulted from CPT-induced cell death. ΔAST on day2 could be a surrogate response biomarker for CPT treatment in RRMM patients. Figure 1 Representative time course of AST, ALT or LDH changes before and after CPT plus thalidomide treatment in response patients Figure 1. Representative time course of AST, ALT or LDH changes before and after CPT plus thalidomide treatment in response patients Table 1 Differences in ΔAST, ΔALT and ΔLDH between response patients (≥PR or ≥MR) and non-response patients (NC/PD) Table 1. Differences in ΔAST, ΔALT and ΔLDH between response patients (≥PR or ≥MR) and non-response patients (NC/PD) Disclosures Wei: Beijing Sunbio Biotech Co., Ltd.: Employment. Yang:Beijing Sunbio Biotech Co., Ltd.: Employment. Zheng:Beijing Sunbio Biotech Co., Ltd.: Employment. Pang:Beijing Sunbio Biotech Co., Ltd.: Employment.
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Okolie, Ugo Chuks, et Idongesit David Udom. « Determinants of Customer Patronage of Fast Food Outlets in Benin City ». Journal of Economics and Management Research 10 (janvier 2022) : 74–99. http://dx.doi.org/10.22364/jemr.10.05.
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This study critically examined the factors influencing customer patronage of fast food outlets in Benin City. Specifically, the independent variables examined include quality of service delivery, brand image and price and how they relate to customer patronage. The study adopted survey research design. The population includes all customers that patronise fast food outlets in Benin City, Edo State. Fifty (50) respondents each were chosen in four fast food outlets namely: Mr. Biggs, Mat Ice, Kada Food and Omega Food to have a sample size of two hundred (200) out of which 188 questionnaires were found useable, amounting to 94%. The data analyses were done using both descriptive and inferential statistics. All analyses were done using Statistical Package for Social Sciences (SPSS 22.0) software. The study revealed that there are positive and significant relationship between the independent variables (service quality and brand image) and customer patronage except price that showed negative and not significant relationship with customer patronage. Based on these findings, the study recommended that fast food operators should continue to maintain high quality service delivery that will enhance the brand image of selected fast food outlets.
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Latagliata, Roberto, Imma Attolico, Malgorzata Monika Trawinska, Isabella Capodanno, Mario Annunziata, Chiara Elena, Luigiana Luciano et al. « Bosutinib in the Real-Life Treatment of Chronic Phase Chronic Myeloid Leukemia (CML) Patients Aged > ; 65 Years Resistant/Intolerant to Frontline Tyrosine-Kynase Inhibitors ». Blood 134, Supplement_1 (13 novembre 2019) : 1649. http://dx.doi.org/10.1182/blood-2019-127029.
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Background Bosutinib is a 2nd generation tyrosine-kinase inhibitor (TKI) active in Chronic Myeloid Leukemia (CML) patients resistant or intolerant to frontline imatinib, dasatinib or nilotinib; the favourable toxicity profile makes bosutinib potentially useful in elderly patients, but at present there are no data in unselected cohorts of these subjects. Aim To highlight this issue, a real-life cohort of 91 patients followed in 21 Italian Centers and treated with bosutinib when aged > 65 years was retrospectively evaluated. Patients The main clinical features of the whole cohort at diagnosis and at baseline of bosutinib treatment are reported in the Table; all patients were in CP when bosutinib was started. Median interval from diagnosis to bosutinib treatment was 49.7 months [interquartile range (IQR) 14.2 - 117.5]. Results Starting dose of bosutinib was 500 mg/day in 20 patients (22.0%), 400 mg/day in 7 patients (7.7%), 300 mg/day in 28 patients (30.8%), 200 mg/day in 34 patients (37.3%) and 100 mg/day in 2 patients (2.2%), respectively. After a median period of treatment of 18.1 months (IQR 9.4 - 27.7) all patients were evaluable for toxicity; on the whole, all grade hematological and extra-hematological toxicities were reported in 12/91 (13.1%) and 45/91 (49.4%) patients, respectively. A grade 3 - 4 hematological toxicity occurred in 5/91 patients (5.4%); a grade 3 - 4 extra-hematological toxicity occurred in 16/91 patients (17.5%). Overall, 46 patients (50.5%) never discontinued bosutinib: a temporary discontinuation < 6 weeks was needed in 19 patients (20.9%) and a temporary discontinuation > 6 weeks in 2 patients (2.2%). A permanent bosutinib discontinuation was needed in the remaining 24 patients (26.4%): in particular, 11 patients (12.1%) permanently discontinued bosutinib due to toxicity (skin rash in 3 cases, gastro-intestinal toxicity in 3 cases, pleural effusion in 2 cases, transaminitis, QTc prolongation and myalgia in 1 case each), 6 patients (6.6%) due to resistance and 7 patients (7.7%) due to other reasons (unrelated death in 6 cases and patient decision in 1 case). As to response, 5 patients (5.5%) were considered too early for assessment (< 3 months of treatment); among the 86 patients evaluable for response, 11 patients (12.7%) did not have any response (including 6 patients who discontinued bosutinib for early toxicity), 4 (4.6%) achieved hematological response only, and 71 (82.5%) achieved Cytogenetic Response (CyR) (Major CyR in 4, Complete CyR in 67). Among the 67 patients in Complete CyR, 58 (67.4% of all 86 evaluable patients) also achieved Molecular Response (MR) [Major MR (MR 3.0) in 19 (22.1%), Deep MR (MR 4.0/4.5) in 39 (45.3%)]. The 3-year Overall Survival and Event-Free Survival of the whole cohort of patients from bosutinib start were 83.0% (CI95% 71.6 - 94.4) (Figure 1) and 59.5% (CI95% 39.9 - 72.1), respectively. Conclusions Our real-life data show that bosutinib is effective, even if initial doses in many cases were lower than recommended, with a favourable safety profile also in elderly patients with important comorbidities resistant/intolerant to previous TKI treatments,: as a consequence, it could play a significant role in the current clinical practise for these frail patients. Disclosures Latagliata: Celgene: Honoraria; Janssen: Honoraria; Novartis: Honoraria; Pfizer: Honoraria. Trawinska:Novartis: Consultancy, Honoraria. Annunziata:Pfizer: Consultancy; Incyte: Consultancy; Novartis: Consultancy. Elena:Novartis: Consultancy; Pfizer: Consultancy. Crugnola:Incyte: Honoraria; Novartis: Honoraria. Bonifacio:Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; BMS: Honoraria. Sgherza:Incyte: Honoraria; Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria. Iurlo:Pfizer: Other: Speaker Honoraria; Incyte: Other: Speaker Honoraria; Novartis: Other: Speaker Honoraria. Breccia:Celgene: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria; Pfizer: Honoraria.
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Shakur, Sophia F., Ali Alaraj, Nasya Mendoza-Elias, Muhammad Osama et Fady T. Charbel. « Hemodynamic characteristics associated with cerebral aneurysm formation in patients with carotid occlusion ». Journal of Neurosurgery 130, no 3 (mars 2019) : 917–22. http://dx.doi.org/10.3171/2017.11.jns171794.
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OBJECTIVEThe pathogenesis of cerebral aneurysms in patients with internal carotid artery (ICA) occlusion is hypothesized to be hemodynamic. For the first time, the authors quantify the hemodynamic characteristics associated with aneurysm formation in patients with ICA occlusion.METHODSRecords of patients with unilateral ICA stenosis or occlusion ≥ 90% who underwent hemodynamic assessment before treatment using quantitative MR angiography were retrospectively reviewed. The patients were classified into 2 groups based on the presence or absence of aneurysms. The hemodynamic parameters of flow volume rate, flow velocity, and wall shear stress (WSS) were measured in each vessel supplying collateral flow—bilateral A1 segments and bilateral posterior communicating arteries—and then compared between the groups.RESULTSA total of 36 patients were included (8 with and 28 without aneurysms). The mean flow (72.3 vs 48.9 ml/min, p = 0.10), flow velocity (21.1 vs 12.7 cm/sec, p = 0.006), and WSS (22.0 vs 12.3 dynes/cm2, p = 0.003) were higher in the A1 segment contralateral to the side of the patent ICA in patients with versus without aneurysms. All de novo or growing aneurysms in our cohort were located on the anterior communicating artery (ACoA) or P1 segment.CONCLUSIONSFlow velocity and WSS are significantly higher across the ACoA in patients who harbor an aneurysm, and de novo or growing aneurysms are often located on collateral vessels. Thus, robust primary collaterals after ICA occlusion may be a contributing factor in cerebral aneurysm formation.
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Yamaoka, K., S. B. Cohen, N. Sugiyama, H. Shi, J. L. Rivas, A. Diehl et J. S. Smolen. « POS0650 PREDICTORS OF DURABLE CLINICAL RESPONSE TO TOFACITINIB 11 MG ONCE DAILY WITH OR WITHOUT METHOTREXATE IN PATIENTS WITH RHEUMATOID ARTHRITIS : POST HOC ANALYSIS OF DATA FROM A PHASE 3b/4 METHOTREXATE WITHDRAWAL STUDY ». Annals of the Rheumatic Diseases 80, Suppl 1 (19 mai 2021) : 563.2–564. http://dx.doi.org/10.1136/annrheumdis-2021-eular.357.
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Background:ORAL Shift, a global Phase 3b/4 non-inferiority study, demonstrated sustained efficacy and safety of tofacitinib modified-release (MR) 11 mg once daily (QD) following methotrexate (MTX) withdrawal in patients with rheumatoid arthritis (RA) who achieved Clinical Disease Activity Index (CDAI) low disease activity (LDA) after treatment with tofacitinib + MTX.1Objectives:To assess predictors of durable clinical response in patients receiving tofacitinib MR 11 mg QD in ORAL Shift.Methods:ORAL Shift (NCT02831855) enrolled patients aged ≥18 years with moderate to severe RA and an inadequate response to MTX. Patients received open-label tofacitinib MR 11 mg QD + MTX for 24 weeks. Patients achieving LDA (CDAI score ≤10) at Week (W)24 entered the 24-week double-blind MTX withdrawal phase and were randomised 1:1 to receive tofacitinib MR 11 mg QD + placebo (tofacitinib monotherapy; ie blinded MTX withdrawal) or continue tofacitinib + MTX. In this post hoc analysis of randomised patients, we assessed predictors of durable response (maintenance of response from W24–48) per CDAI LDA and remission (CDAI score ≤2.8) criteria. All covariates were initially assessed for significance in a univariate logistic regression. Highly correlated covariates were reviewed to assess which would be removed prior to modelling in a multivariable logistic regression. Remaining significant (p≤0.10) covariates in the univariate regression were selected in the model using a stepwise selection process with p≤0.15 entry and p≤0.05 stay criteria. From the final model, estimated odds ratios (ORs) with 95% confidence intervals (CIs) are presented.Results:In the double-blind phase of ORAL Shift, durable CDAI LDA and remission rates were: 66.2% and 14.7%, respectively, with tofacitinib + MTX (N=266); and 55.3% and 11.0%, respectively, with tofacitinib + placebo (N=264) (Table 1). In the multivariable analysis, five patient covariates significantly predicted durable CDAI LDA (Figure 1; discussed hereafter). Each unit increase in CDAI score at W24 reduced the likelihood of maintaining CDAI LDA by 22.0%. Each unit increase in C-reactive protein (CRP) at W24 increased the likelihood of maintaining CDAI LDA by 4.0%; this may have been due to imbalanced CRP levels at W24 (randomisation) between treatment groups (Figure 1, footnote c). The odds of durable CDAI LDA were 53.0% lower in the US vs Europe and 61.0% lower in the US vs ‘other’ regions. Each unit increase in baseline Health Assessment Questionnaire-Disability Index (HAQ-DI) score reduced the odds of durable CDAI LDA by 34.0%. Patients receiving tofacitinib + MTX had 66.0% greater odds of durable CDAI LDA vs patients receiving tofacitinib + placebo. CDAI at W24 was the only significant predictor of durable CDAI remission in the multivariable analysis: OR (95% CI) 0.32 (0.24, 0.43); p<0.0001. Each unit increase in CDAI score at W24 reduced the odds of durable CDAI remission by 68.0%.Table 1.Durable CDAI LDA and remissiona in patients receiving tofacitinib MR 11 mg QD with MTX or placebo in the double-blind phase of ORAL ShiftTofacitinib + MTX(N=266)Tofacitinib + placebo(N=264)Durable CDAI LDA, n (%)176 (66.2)146 (55.3)Durable CDAI remission, n (%)39 (14.7)29 (11.0)aDurable CDAI LDA or remission was defined as achievement of LDA (CDAI score ≤10) or remission (CDAI score ≤2.8), respectively, at W24–48N, number of patients in each group; n, number of patients achieving outcomeConclusion:This post hoc analysis of data from ORAL Shift found that CDAI and CRP at W24, geographic region, baseline HAQ-DI and treatment could be predictors for durable CDAI LDA. As these findings were limited to patients who achieved CDAI LDA at W24 with tofacitinib MR 11 mg QD + MTX, additional data in the general patient population need to be investigated.References:[1]Cohen et al. Lancet Rheumatol 2019; 1: E23-34.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Sarah Piggott, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Kunihiro Yamaoka Speakers bureau: Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, Takeda, Consultant of: Actelion, Astellas, Chugai, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Nippon Shinyaku, Pfizer Inc, Takeda, Stanley B. Cohen Consultant of: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Genentech, Gilead Sciences, Pfizer Inc, Naonobu Sugiyama Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Jose Luis Rivas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Josef S. Smolen Consultant of: AbbVie, AstraZeneca, Celgene, Celltrion, Chugai, Eli Lilly, Gilead Sciences, ILTOO, Janssen, Novartis-Sandoz, Pfizer Inc, Roche, Samsung, Sanofi, Grant/research support from: AbbVie and AstraZeneca
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Kakegawa, Tatsuya, Katsutoshi Sugimoto, Kazuhiro Saito, Daisuke Yunaiyama, Yoichi Araki, Takuya Wada, Hiroshi Takahashi, Yu Yoshimasu, Hirohito Takeuchi et Takao Itoi. « Favorable liver and skeletal muscle changes in patients with MASLD and T2DM receiving glucagon-like peptide-1 receptor agonist : A prospective cohort study ». Medicine 103, no 23 (7 juin 2024) : e38444. http://dx.doi.org/10.1097/md.0000000000038444.
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To investigate changes in skeletal muscle mass and fat fraction in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) undergoing treatment with Semaglutide for 6months. This single-arm pilot study included 21 patients with MASLD who received semaglutide for T2DM. Body weight, metabolic parameters, liver enzymes, fibrosis markers, skeletal muscle index (cm2/m2), and fat fraction (%) at the L3 level using the two-point Dixon method on magnetic resonance imaging (MRI), as well as liver steatosis and liver stiffness assessed using MRI-based proton density fat fraction (MRI-PDFF) and MR elastography, respectively, were prospectively examined before and 6 months after semaglutide administration. The mean age of the patients was 53 years and 47.6% were females. The median liver steatosis-fraction (%) and skeletal muscle steatosis-fraction values (%) significantly decreased (22.0 vs 12.0; P = .0014) and (12.8 vs 9.9; P = .0416) at baseline and 6 months, respectively, while maintaining muscle mass during treatment. Semaglutide also dramatically reduced hemoglobin A1c (%) (6.8 vs 5.8, P = .0003), AST (IU/L) (54 vs 26, P < .0001), ALT (IU/L) (80 vs 34, P = .0004), and γ-GTP (IU/L) levels (64 vs 34, P = .0007). Although not statistically significant, Body weight (kg) (79.9 vs 77.4), body mass index (BMI) (kg/m2) (28.9 vs 27.6), and liver stiffness (kPa) (28.9 vs 27.6) showed a decreasing trend. Fibrosis markers such as M2BPGi, type IV collagen, and skeletal muscle area did not differ. Semaglutide demonstrated favorable effects on liver and skeletal muscle steatosis, promoting improved liver function and diabetic status.
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Martynowicz, Paweł, Georgios M. Katsaounis et Spyridon A. Mavrakos. « Comparison of Floating Offshore Wind Turbine Tower Deflection Mitigation Methods Using Nonlinear Optimal-Based Reduced-Stroke Tuned Vibration Absorber ». Energies 17, no 6 (21 mars 2024) : 1507. http://dx.doi.org/10.3390/en17061507.
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Tower fatigue and strength are crucial operational concerns of floating offshore wind turbines (FOWTs) due to the escalation of the vibration phenomena observed on these structures as compared to land-based ones. FOWT towers are excited by wave and wind polyperiodic disturbances yielding continual transient states of structural vibration that are challenging for vibration mitigation systems. Thus, the paper investigates a novel implementation of nonlinear optimal-based vibration control solutions for the full-scale, tension leg platform (TLP)-based, NREL 5MW wind turbine tower-nacelle model with a 10-ton tuned vibration absorber (TVA), equipped with a magnetorheological (MR) damper, located at the nacelle. The structure is subjected to excessive wave and wind excitations, considering floating platform motions derived from model experiments in a wave tank. The MR damper operates simultaneously with an electromagnetic force actuator (forming a hybrid TVA) or independently (a semiactive TVA). The study includes both actuators’ nonlinearities and dynamics, whereby the former are embedded in the Hamilton-principle-based nonlinear control solutions. The TVA is tuned either to the NREL 5MW tower-nacelle 1st bending mode frequency (TVA-TN) or to the TLP surge frequency (TVA-TLP). The optimal control task was redeveloped concerning the TVA stroke and transient vibration minimisation, including the implementation of the protected structure’s acceleration and relative displacement terms, as well as the nonzero velocity term in the quality index. The regarded model is embedded in a MATLAB/Simulink environment. On the basis of the obtained results, the TVA-TN solution is by far superior to the TVA-TLP one. All the regarded TVA-TN solutions provide a tower deflection safety factor of ca. 2, while reference systems without any vibration reduction solutions or with a passive TVA-TLP are at risk of tower structural failure as well as the hybrid TVA-TLP system. The obtained TVA stroke reductions of 25.7%/22.0% coincide with 3.6%/10.3% maximum tower deflection reductions for the semiactive/hybrid TVA-TN case (respectively) with regard to the previously developed approaches. Moreover, these reductions are obtained due to the sole control algorithm enhancement; thus, no additional resources are necessary, while this attainment is accompanied by a reduction in the required MR damper force. The lowest obtained TVA stroke amplitude of 1.66 m is guaranteed by the newly introduced semiactive control. Its hybrid equivalent ensures 8% lower primary structure deflection amplitude and reduced nacelle acceleration levels thanks to the utilisation of the force actuator of the relatively low power (ca. 6 kW); the trade-off is an increased TVA stroke amplitude of 2.19 m, which, however, is the lowest among all the tested hybrid solutions. The analysed reference passive TVA systems, along with a modified ground-hook hybrid solution, can hardly be implemented in the nacelle (especially along the demanding side–side direction). The latter, being the well-proven hybrid solution for steady-state tower deflection minimisation, yielded unsatisfactory results. The achievements of the study may be used for an effective design of a full-scale vibration reduction system for the TLP-based floating wind turbine structure.
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Feldman, Paul L. « Insights into the Chemical Discovery of Remifentanil ». Anesthesiology 132, no 5 (1 mai 2020) : 1229–34. http://dx.doi.org/10.1097/aln.0000000000003170.
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Abstract Design, Synthesis, and Pharmacological Evaluation of Ultrashort- to Long-acting Opioid Analgetics. By Feldman PL, James MK, Brackeen MF, Bilotta JM, Schuster SV, Lahey AP, Lutz MW, Johnson MR, Leighton HJ. J Med Chem 1991; 34:2202-8. Copyright 1991 American Chemical Society. Reprinted with permission. In an effort to discover a potent ultrashort-acting µ-opioid analgetic that is capable of metabolizing to an inactive species independent of hepatic function, several classes of 4-anilidopiperidine analgetics were synthesized and evaluated. One series of compounds displayed potent µ-opioid agonist activity with a high degree of analgesic efficacy and an ultrashort to long duration of action. These analgetics, 4-(methoxycarbonyl)-4-[1-oxopropyl)phenylamino]-1-piperidinepropanoic acid alkyl esters, were evaluated in vitro in the guinea pig ileum for µ-opioid activity, in vivo in the rat tail withdrawal assay for analgesic efficacy and duration of action, and in vitro in human whole blood for their ability to be metabolized in blood. Compounds in this series were all shown to be potent µ agonists in vitro, but depending upon the alkyl ester substitution, the potency and duration of action in vivo varied substantially. The discrepancies between the in vitro and in vivo activities and variations in duration of action are probably due to different rates of ester hydrolysis by blood esterase(s). The [structure–activity relationships] with respect to analgesic activity and duration of action as a function of the various esters synthesized is discussed. It was also demonstrated that the duration of action for the ultrashort-acting analgetic, 8, does not change upon prolonged infusion or administration of multiple bolus injections.
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Ronchev, Yovko, Dora Terzieva et Eduard Tilkiyan. « The role of serum levels of anti-phospholipase A2 receptor antibodies in the diagnosis of primary membranous nephropathy. » Folia Medica 63, no 5 (31 octobre 2021) : 692–96. http://dx.doi.org/10.3897/folmed.63.e55460.
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Introduction: Primary membranous nephropathy (PMN) is one of the most common causes of nephrotic syndrome in adults. The disease process is probably initiated by the binding of circulating autoantibodies to target podocyte antigens. In 2009, Beck et al. found that phospholipase A2 receptor (PLA2R1) was expressed on human podocytes in patients with PMN. Recent evidence suggests that PLA2R1 autoantibodies play an important role in the diagnosis of PMN. Aim: The aim of the present study was to compare the serum levels of anti-PLA2R1 in patients with PMN, second MN (SMN), other nephropathies (ON), and healthy controls (HC). Materials and methods: The study included 52 patients with PMN, 12 patients with SMN, 49 patients with ON, and 50 healthy controls. The serum concentration of anti-PLA2R1 was determined with ELISA kit (Anti-PLA2R ELISA, IgG, EUROIMMUN, Lübeck, Germany) using MR-96A microplate Reader (MINDRAY). Statistical analysis was performed with SPSS v.22.0. Results: There was significant difference in the serum anti-PLA2R1 concentrations between patient groups and HC (p<0.0001). Compared to HC, the median anti-PLA2R1 level in the PMN group was significantly higher (4.8 RU/ml vs. 34.9 RU/ml, p=0.001), in the ON group it was lower (2.1 RU/ml, p=0.002) and did not differ in patients with SMN (2.9 RU/ml, p=0.193). The anti-PLA2R1 serum levels were significantly higher in the PMN group than in the SMN (p=0.015) and ON (p<0.001) groups. Conclusions: Our results showed that anti-PLA2R1 is significantly increased in patients with PMN. We can conclude that the anti-PLA2R1 serum concentration may be used as a beneficial biomarker for distinguishing PMN from other membranous nephropathies.
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van den Berg, Lucie A., Olvert A. Berkhemer, Puck S. S. Fransen, Debbie Beumer, Hester Lingsma, Charles B. M. Majoie, Diederik W. J. Dippel et al. « Economic Evaluation of Endovascular Treatment for Acute Ischemic Stroke ». Stroke 53, no 3 (mars 2022) : 968–75. http://dx.doi.org/10.1161/strokeaha.121.034599.
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Background and Purpose: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. Methods: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0–2) and the extra cost per quality-adjusted life year gained. Results: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, −$16 839 [95% CI, −$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%–22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04–0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. Conclusions: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: https://www.trialregister.nl/trial/695 ; Unique identifier: NL695. URL: https://www.isrctn.com ; Unique identifier: ISRCTN10888758.
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Sheehan, Jason P., Britney Popp, Stephen Monteith, Sushila Toulmin, Jennifer Tomlinson, Jessica Martin, Christopher P. Cifarelli, Dae-Hee Lee et Deric M. Park. « Trans sodium crocetinate : functional neuroimaging studies in a hypoxic brain tumor ». Journal of Neurosurgery 115, no 4 (octobre 2011) : 749–53. http://dx.doi.org/10.3171/2011.5.jns101954.
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Object Intratumoral hypoxia is believed to be exhibited in high-grade gliomas. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion to hypoxic tissues. In this research, the authors use oxygen-sensitive PET studies to evaluate the extent of hypoxia in vivo in a glioblastoma model and the effect of TSC on the baseline oxygenation of the tumor. Methods The C6 glioma cells were stereotactically implanted in the right frontal region of rat brains. Formation of intracranial tumors was confirmed on MR imaging. Animals were injected with Copper(II) diacetyl-di(N4-methylthiosemicarbazone) (Cu-ATSM) and then either TSC or saline (6 rats each). Positron emission tomography imaging was performed, and relative uptake values were computed to determine oxygenation within the tumor and normal brain parenchyma. Additionally, TSC or saline was infused into the animals, and carbonic anhydrase 9 (CA9) and hypoxia-inducing factor–1α (HIF-1α) protein expression were measured 1 day afterward. Results On PET imaging, all glioblastoma tumors demonstrated a statistically significant decrease in uptake of Cu-ATSM compared with the contralateral cerebral hemisphere (p = 0.000002). The mean relative uptake value of the tumor was 3900 (range 2203–6836), and that of the contralateral brain tissue was 1017 (range 488–2304). The mean relative hypoxic tumor volume for the saline group and TSC group (6 rats each) was 1.01 ± 0.063 and 0.69 ± 0.062, respectively (mean ± SEM, p = 0.002). Infusion of TSC resulted in a 31% decrease in hypoxic volume. Immunoblot analysis revealed expression of HIF-1α and CA9 in all tumor specimens. Conclusions Some glioblastomas exhibit hypoxia that is demonstrable on oxygen-specific PET imaging. It appears that TSC lessens intratumoral hypoxia on functional imaging. Further studies should explore relative hypoxia in glioblastoma and the potential therapeutic gains that can be achieved by lessening hypoxia during delivery of adjuvant treatment.