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991.
Gaëlle Oka Valérie Roussel-Robert Clara Levivien Isabelle Lopez Rémi Pieragostini 《Haemophilia》2023,29(3):709-715
Introduction
Since the approval by the EMA of emicizumab for the care of severe haemophilia A without inhibitor, most of the patients of our haemophilia treatment centre started this new treatment. Thanks to the setting of a therapeutic patient education program including three pharmaceutical consultations (PC), we could follow patients’ lifestyle evolution.Aim
The study aimed to assess the perceived clinical evolution, quality of life and treatment satisfaction of patients after 1 year of emicizumab therapy in real-life settings.Methods
The study was observational, retrospective and monocentric. Every patient over 18 years old receiving emicizumab from June 2020 and who underwent the 3 PC until March 2022 were included. The clinical evolution was self-estimated by patients with zero-to-six scales before versus 1 year after emicizumab, according to the following parameters: general health state, pain and bleedings (spontaneous or post-traumatic, and patients’ identification ability). Patients’ quality of life was also estimated with the EQ-5D-3L survey. Their satisfaction, graduated with a zero-to-ten scale, and treatment management were reported during the third PC.Results
Thirty-eight patients were enrolled. Their general health state improved significantly (p = .0023) with an EQ-5D-3L score at 69.6 (±19.4) out of 100. Although chronic pains remained a persistent issue for 33 (86.8%) patients, their intensity was significantly decreasing after 1 year. Perceived frequency of bleedings was significantly reduced too. On average, the satisfaction of emicizumab therapy was 9.1 (± 1.02) out of 10.Conclusion
After 1 year of emicizumab therapy, the general health state estimated by patients improved, the pain and the perceived frequency of bleedings diminished. Overall, this treatment received a high patients’ satisfaction rate. 相似文献992.
Learning increases human electroencephalographic coherence during subsequent slow sleep oscillations 总被引:2,自引:0,他引:2
Mölle M Marshall L Gais S Born J 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(38):13963-13968
Learning is assumed to induce specific changes in neuronal activity during sleep that serve the consolidation of newly acquired memories. To specify such changes, we measured electroencephalographic (EEG) coherence during performance on a declarative learning task (word pair associations) and subsequent sleep. Compared with a nonlearning control condition, learning performance was accompanied with a strong increase in coherence in several EEG frequency bands. During subsequent non-rapid eye movement sleep, coherence only marginally increased in a global analysis of EEG recordings. However, a striking and robust increase in learning-dependent coherence was found when analyses were performed time-locked to the occurrence of slow oscillations (<1 Hz). Specifically, the surface-positive half-waves of the slow oscillation resulting from widespread cortical depolarization were associated with distinctly enhanced coherence after learning in the slow-oscillatory, delta, slow-spindle, and gamma bands. The findings identify the depolarizing phase of the slow oscillations in humans as a time period particularly relevant for a reprocessing of memories in sleep. 相似文献
993.
PURPOSE: The aim of this study was to compare tissue harmonic imaging (THI) and conventional (fundamental) sonography in the evaluation of the scapholunate ligament (SLL). METHODS: The bilateral SLL of 3 patients with unilateral SLL rupture and the bilateral SLL of 20 volunteers without history of trauma were examined. THI findings were compared with conventional sonographic findings. RESULTS: On conventional sonographic evaluation of 43 normal wrists, the dorsal component of the SLL was partially visible in 10 of the 43 normal wrists (23%) and was completely visible in 33 of 43 (77%) normal wrists. Using THI, the SLL was visible in its entirety in 39 of 43 normal wrists (91%) and was partially visible in 4 of 43 normal wrists (9%). The mean scapholunate distance was 3.3 mm (range, 2.9-4.5 mm) in normal wrists. THI improved visualization of SLL continuity and demonstration of its fibrillar echotexture. In the 3 wrists with clinical and/or radiological evidence of SLL rupture, the SLL was not visible with conventional sonography nor THI; the mean scapholunate distance was 6.1 mm (range, 5.6-6.8 mm). CONCLUSIONS: THI improves visualization of the SLL. 相似文献
994.
Uterine leiomyomas, or fibroids, are the most common tumors of the myometrium. The ELT3 cell line, derived from Eker rat leiomyoma, has been successfully used as a model for the study of leiomyomas. We have demonstrated previously the potent mitogenic properties of the peptidic hormone endothelin (ET)-1 in this cell line. Here we investigated the antiapoptotic effect of ET-1 in ELT3 cells. We found that 1) serum starvation of ELT3 cells induced an apoptotic process characterized by cytochrome c release from mitochondria, caspase-3/7 activation, nuclei condensation and DNA fragmentation; 2) ET-1 prevented the apoptotic process; and 3) this effect of ET-1 was fully reproduced by ETB agonists. In contrast, no antiapoptotic effect of ET-1 was observed in normal myometrial cells. A pharmacological approach showed that the effect of ET-1 on caspase-3/7 activation in ELT3 cells was not dependent on phosphatidylinositol 3-kinase, ERK1/2, or phospholipase D activities. However, inhibitors of sphingosine kinase-1 (SphK1), dimethylsphingosine and threo-dihydrosphingosine, reduced the effect of ET-1 by about 50%. Identical results were obtained when SphK1 expression was down-regulated in ELT3 cells transfected with SphK1 small interfering RNA. Furthermore, serum starvation induced a decrease in SphK1 activity that was prevented by ET-1 without affecting the level of SphK1 protein expression. Finally, sphingosine 1-phosphate, the product of SphK activity, was as efficient as ET-1 in inhibiting serum starvation-induced caspase-3/7 activation. Together, these results demonstrate that ET-1 possesses a potent antiapoptotic effect in ELT3 cells that involves sphingolipid metabolism through the activation of SphK1. 相似文献
995.
Simon Cauchemez Laura Temime Alain-Jacques Valleron Emmanuelle Varon Guy Thomas Didier Guillemot Pierre-Yves Boëlle 《BMC infectious diseases》2006,6(1):14-10
Background
Recent trends of pneumococcal colonization in the United States, following the introduction of conjugate vaccination, indicate that non-vaccine serotypes tend to replace vaccine serotypes. The eventual extent of this replacement is however unknown and depends on serotype-specific carriage and transmission characteristics. 相似文献996.
Gwena?lle Douaud Adrian R. Groves Christian K. Tamnes Lars Tjelta Westlye Eugene P. Duff Andreas Engvig Kristine B. Walhovd Anthony James Achim Gass Andreas U. Monsch Paul M. Matthews Anders M. Fjell Stephen M. Smith Heidi Johansen-Berg 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(49):17648-17653
Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8–85 y) reveals a largely—but not only—transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer’s disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer’s disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer’s disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.Many phylogenetic or ontogenetic models attempt to relate development and aging at genetic, molecular, or cognitive systems levels (1–4). In neuroscience, one of the most popular hypotheses in this respect postulates that the process of healthy age-related brain decline mirrors developmental maturation. This concept was first introduced in 1881 as a “loi de régression” (Ribot’s law) when Théodule Ribot, a French philosopher, observed that the destruction of memories progresses in reverse order to that of their formation: from the unstable to the stable, from the newly formed memories to older “sensory, instinctive” memories (5). More generally, this hypothesis postulates that the sequence of events associated with brain decline should present itself in reverse order to the series of events related to brain development, with brain regions thought to develop relatively late—at both ontogenetic and phylogenetic levels—also degenerating relatively early (2, 6, 7).One way of tracking this hypothesized mirroring pattern of development and aging in the human brain is to use the information provided at a macroscopic level by structural MRI in large-scale, lifespan human populations. Although structural MRI does not distinguish between the various cellular mechanisms underpinning development and aging processes [e.g., dendritic and synaptic remodeling, neurogenesis and neuronal death, astrogliosis, (de)myelination], this technique is sensitive to detect the overall contribution of these mechanisms to macroscopic age-related changes in brain structure (8–10).In 2000, Raz (11) presented for the first time MRI data suggesting that the chronological order of completion of intracortical fibers myelination was associated with age-related differences in cortical volume. In particular, Raz (12) later noted that “the pattern of differential brain aging suggests that phylogenetically newer and ontogenetically less precocious brain structures such as association cortices and the neostriatum show increased vulnerability to the effects of aging … follow(ing) the rule of (phylogenetically and ontogenetically) last-in, first-out” (12). Direct and intrinsic evidence for a clear link between brain structural development and aging lending support to this evolutionary–developmental “retrogenesis” model [or the “last-in, first-out” model as Raz (12) and others call it] is needed, however. Most of the structural imaging studies investigating relationships between development and aging have so far led to different, and sometimes contradictory, results (13, 14). One possible explanation for this inconsistency is that these studies have tested only one specific pattern of age-related change and have focused on age subgroups or on predefined regions of the brain.Here, we took a purely data-driven approach to assess the intersubject brain structure variability among 484 healthy participants covering most of the lifespan (8–85 y). We analyzed the structural brain images of these healthy subjects using a linked independent component analysis (ICA) (SI Materials and Methods) (15). This approach provides an automatic decomposition of the images into spatial components characterizing the intersubject brain structural variability, i.e., each spatial component represents a mode of variation of brain structure across all participants. 相似文献
997.
BACKGROUND: The preparation of platelet (PLT) concentrates (PCs) from PLT-rich plasma (PRP) requires that whole blood (WB) be processed within 8 hours of collection. Increasing WB storage time to 24 hours would be logistically attractive. This study compares the in vitro quality of blood components prepared from WB stored for 8 and 24 hours at room temperature before processing with the PRP method. STUDY DESIGN AND METHODS: WB units were collected from ABO-matched blood donors. To reduce individual variations, paired donations were drawn in parallel, pooled, and split back in the collection bag. One unit was held for 6 to 8 hours and the other for 22 to 24 hours at 20 to 24 degrees C. Prestorage leukoreduced components were prepared with the PRP as intermediate product and analyzed during storage. RESULTS: RBC units prepared after an 8- or 24-hour hold were comparable in terms of hemolysis, sodium, pH, and ATP levels. RBC 2,3- diphosphoglycerate (2,3-DPG) was significantly lower in RBCs prepared from 24-hour hold donations immediately after processing but not after 20 days of storage. Residual white blood cells were approximately fivefold higher (p < 0.05) in 24-hour RBC units. For PCs, measurements for glucose, ATP, lactate, pH, extent of shape change, hypotonic shock response, and CD62p activation were similar. No differences were observed in the von Willebrand factor, factor (F)V, FVIII, and fibrinogen content of fresh-frozen plasma. CONCLUSIONS: The decrease in FVIII and RBC 2,3-DPG can be acceptable as a compromise to improve blood component logistics, but leukoreduction efficiency must be improved before considering the adoption of an overnight storage of WB before PRP processing. 相似文献
998.
Thibault L Beauséjour A de Grandmont MJ Long A Goldman M Chevrier MC 《Transfusion》2006,46(12):2115-2121
BACKGROUND: Transfusion of blood products to immunoglobulin A (IgA)-deficient patients who have developed IgA antibodies can result in serious adverse reactions. To prepare compatible blood components for these patients, blood centers usually maintain a list of IgA-deficient blood donors. An in-house enzyme-linked immunosorbent assay (ELISA) was used to identify new IgA-deficient blood donors. STUDY DESIGN AND METHODS: An in-house ELISA was used to screen blood samples. IgA-deficient samples, defined as an IgA level below 0.05 mg per dL, were sent to the American Red Cross for confirmatory testing. RESULTS: Seventy-three confirmed IgA-deficient blood donors were identified among 38,759 screened blood donor samples (frequency, 1:531). IgA antibodies were found in 39 of these 73 blood donors (53%), although only 9 donors had a history of adult IgA exposure (transfusion or pregnancy). CONCLUSIONS: With a simple in-house ELISA, 73 blood donors were identified as IgA-deficient. From this number, 34 donors, without detectable anti-IgA in their plasma, were added to our IgA-deficient blood donor panel to maximize the management of our inventory of IgA-deficient frozen blood components. 相似文献
999.
General catalytic deficiency of hepatitis C virus RNA polymerase with an S282T mutation and mutually exclusive resistance towards 2'-modified nucleotide analogues 下载免费PDF全文
Dutartre H Bussetta C Boretto J Canard B 《Antimicrobial agents and chemotherapy》2006,50(12):4161-4169
The hepatitis C virus (HCV) RNA-dependent RNA polymerase NS5B is an important target for antiviral therapies. NS5B is able to initiate viral RNA synthesis de novo and then switch to a fast and processive RNA elongation synthesis mode. The nucleotide analogue 2'-C-methyl CTP (2'-C-Me-CTP) is the active metabolite of NM283, a drug currently in clinical phase II trials. The resistance mutation S282T can be selected in HCV replicon studies. Likewise, 2'-O-Me nucleotides are active both against the purified polymerase and in replicon studies. We have determined the molecular mechanism by which the S282T mutation confers resistance to 2'-modified nucleotide analogues. 2'-C-Me-CTP is no longer incorporated during the initiation step of RNA synthesis and is discriminated 21-fold during RNA elongation by the NS5B S282T mutant. Strikingly, 2'-O-methyl CTP sensitivity does not change during initiation, but the analogue is no longer incorporated during elongation. This mutually exclusive resistance mechanism suggests not only that "2'-conformer" analogues target distinct steps in RNA synthesis but also that these analogues have interesting potential in combination therapies. In addition, the presence of the S282T mutation induces a general cost in terms of polymerase efficiency that may translate to decreased viral fitness: natural nucleotides become 5- to 20-fold less efficiently incorporated into RNA by the NS5B S282T mutant. As in the case for human immunodeficiency virus, our results might provide a mechanistic basis for the rational combination of drugs for low-fitness viruses. 相似文献
1000.
Armelle Marais Chantal Faure Gwenaëlle Comont Thierry Candresse Elodie Stempien Marie-France Corio-Costet 《Viruses》2021,13(3)
Neofusicoccum parvum is a fungal plant-pathogen belonging to the family Botryosphaeriaceae, and is considered one of the most aggressive causal agents of the grapevine trunk disease (GTD) Botryosphaeria dieback. In this study, the mycovirome of a single strain of N. parvum (COLB) was characterized by high throughput sequencing analysis of total RNA and subsequent bioinformatic analyses. Contig annotations, genome completions, and phylogenetic analyses allowed us to describe six novel mycoviruses belonging to four different viral families. The virome is composed of two victoriviruses in the family Totiviridae, one alphaendornavirus in the family Endornaviridae, two mitoviruses in the family Mitoviridae, and one narnavirus belonging to the family Narnaviridae. The presence of the co-infecting viruses was confirmed by sequencing the RT-PCR products generated from total nucleic acids extracted from COLB. This study shows that the mycovirome of a single N. parvum strain is highly diverse and distinct from that previously described in N. parvum strains isolated from grapevines. 相似文献