912 resultados para Back-arc Extension


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α-Crystallins, initially described as the major structural proteins of the lens, belong to the small heat shock protein family. Apart from their function as chaperones, α-crystallins are involved in the regulation of intracellular apoptotic signals. αA- and αB-crystallins have been shown to interfere with the mitochondrial apoptotic pathway triggering Bax pro-apoptotic activity and downstream activation of effector caspases. Differential regulation of α-crystallins has been observed in several eye diseases such as age-related macular degeneration and stress-induced and inherited retinal degenerations. Although the function of α-crystallins in healthy and diseased retina remains poorly understood, their altered expression in pathological conditions argue in favor of a role in cellular defensive response. In the Rpe65(-/-) mouse model of Leber's congenital amaurosis, we previously observed decreased expression of αA- and αB-crystallins during disease progression, which was correlated with Bax pro-death activity and photoreceptor apoptosis. In the present study, we demonstrated that α-crystallins interacted with pro-apoptotic Bax and displayed cytoprotective action against Bax-triggered apoptosis, as assessed by TUNEL and caspase assays. We further observed in staurosporine-treated photoreceptor-like 661W cells stably overexpressing αA- or αB-crystallin that Bax-dependent apoptosis and caspase activation were inhibited. Finally, we reported that the C-terminal extension domain of αA-crystallin was sufficient to provide protection against Bax-triggered apoptosis. Altogether, these data suggest that α-crystallins interfere with Bax-induced apoptosis in several cell types, including the cone-derived 661W cells. They further suggest that αA-crystallin-derived peptides might be sufficient to promote cytoprotective action in response to apoptotic cell death.

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CONTEXT: The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years. OBJECTIVE: The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure. DESIGN, SETTING, AND PARTICIPANTS: This was a multicenter, international, open-label study of 4550 women. INTERVENTION: Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (crossover). MAIN OUTCOME MEASURES: Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety data are reported. RESULTS: Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover) after denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the crossover group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below the rates projected for a virtual placebo cohort. In the crossover group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of osteonecrosis of the jaw confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture. CONCLUSION: Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low.

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OBJECTIVE: To compare image quality of a standard-dose (SD) and a low-dose (LD) cervical spine CT protocol using filtered back-projection (FBP) and iterative reconstruction (IR). MATERIALS AND METHODS: Forty patients investigated by cervical spine CT were prospectively randomised into two groups: SD (120 kVp, 275 mAs) and LD (120 kVp, 150 mAs), both applying automatic tube current modulation. Data were reconstructed using both FBP and sinogram-affirmed IR. Image noise, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were measured. Two radiologists independently and blindly assessed the following anatomical structures at C3-C4 and C6-C7 levels, using a four-point scale: intervertebral disc, content of neural foramina and dural sac, ligaments, soft tissues and vertebrae. They subsequently rated overall image quality using a ten-point scale. RESULTS: For both protocols and at each disc level, IR significantly decreased image noise and increased SNR and CNR, compared with FBP. SNR and CNR were statistically equivalent in LD-IR and SD-FBP protocols. Regardless of the dose and disc level, the qualitative scores with IR compared with FBP, and with LD-IR compared with SD-FBP, were significantly higher or not statistically different for intervertebral discs, neural foramina and ligaments, while significantly lower or not statistically different for soft tissues and vertebrae. The overall image quality scores were significantly higher with IR compared with FBP, and with LD-IR compared with SD-FBP. CONCLUSION: LD-IR cervical spine CT provides better image quality for intervertebral discs, neural foramina and ligaments, and worse image quality for soft tissues and vertebrae, compared with SD-FBP, while reducing radiation dose by approximately 40 %.

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La relation thérapeutique jour un rôle primordial dans le processus du rétablissement des patients. Il est important que les outils probants soient suffisamment bien ajustés pour faciliter le travail thérapeutique. Le projet Back to the patient, développé en collaboration étroite avec l'équipe de TECAPP technologies applications (www.tecapp.ch), vise à offrir des outils informatiques utilisables sur la tablette ou téléphone portable pour soutenir la relation thérapeutique dans le cadre de l'évaluation des besoins de santé et des soins.

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Spherical carbon coated iron particles of nanometric diameter in the 510 nm range have been produced by arc discharge at near-atmospheric pressure conditions (using 58·10 4 Pa of He). The particles exhibit a crystalline dense iron core with an average diameter 7.4 ± 2.0 nm surrounded by a sealed carbon shell, shown by transmission electron microscopy (TEM), selected-area diffrac- tion (SAED), energy-dispersive X-ray analysis (STEM-EDX) and electron energy loss spectroscopy (EELS). The SAED, EDX and EELS results indicate a lack of traces of core oxidized phases showing an efficient protection role of the carbon shell. The magnetic properties of the nanoparticles have been investigated in the 5300 K temperature range using a superconducting quantum interference device (SQUID). The results reveal a superparamagnetic behaviour with an average monodomain diameter of 7.6 nm of the nanoparticles. The zero field cooled and field cooled (ZFC-FC)magnetization curves show a blocking temperature (TB)at room temperature very suitable for biomedical applications (drug delivery, magnetic resonance imaging MRI, hyperthermia).