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Graefe's Archive for Clinical and Experimental Ophthalmology - To describe and present results after a technique for cataract surgery combined with explantation of an iris-fixated phakic...  相似文献   
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Nude mice have been extensively used to investigate the potency of tissue engineering strategies for bone repair. However, the contribution of pro‐inflammatory and proregenerative stimuli of the host for the process of new bone formation and integration remains poorly understood. In this study, ectopic bone formation was investigated in nude (Nu) versus wild‐type (WT) mice. Calcium phosphate (CaP) scaffolds (CopiOs [Zimmer] and Bio‐Oss [Geistlich]) were loaded with different concentrations of rhBMP6 (40, 120, and 240 ng/mm3 rhBMP6) and implanted subcutaneously in Nu (BALB/c and NMR1) and WT (BALB/c and c57BL/6) mice. CaP scaffolds loaded with rhBMP6 did not form bone in WT mice. However, in Nu mice, 40 ng/mm3 rhBMP6 was sufficient to generate relevant volumes of new bone at 6 weeks after implantation. Looking into potential underlying mechanisms, TNF‐α blocking antibodies were injected intraperitoneally but could not restore bone formation. Also, mouse periosteal cells (mPDCs) seeded in CopiOs loaded with rhBMP6 did not significantly improve the outcome. Abrogation of bone formation was associated with dense cellular infiltration, in particular with the presence of CD3+ T‐lymphocytes. To probe a correlation between calcium ions and impaired bone formation in WT mice, type 1 collagen gels were loaded with rhBMP6 and calcium chloride and injected subcutaneously. These gels generated new bone in WT mice despite the increased percentage of CD3+ cells at Day 3 after implantation as compared with control gels. Overall, this study illustrated the negative effect of the inflammatory host response on the bone‐forming capacity of rhBMP6 coated on bioceramic scaffolds.  相似文献   
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Objective: In DSM-5, Section III, the Level of Personality Functioning (LPF) was proposed as a severity index of personality disorders (PDs), but as it reflects both trait-like (availability) and state-like (accessibility) features, of which, moreover, the relationship with the experience of patients is unclear, we critically examined LPF in patients with general psychopathology. Method: This study compared the validity of the direct Inventory of Personality Organization (IPO), and the indirect Differentiation-Relatedness Scale (DRS) LPF-measure, in relation to measures of intrapersonal and interpersonal functioning. The sample consisted of 70 inpatients with general psychopathology and no primary PDs. Associations of both measures with DSM-PDs were examined, with and without controlling for clinical distress. Results: The IPO was significantly related to age and clinical distress. When controlling for clinical distress, the IPO was still associated with cluster A (odd) and B (erratic) PD features, high levels of self-criticism, conflict in relationships and low levels of adaptive coping strategies. The DRS was only related to the schizotypical PD. Conclusions: In patients with general psychopathology, both the IPO and the DRS, appear to have limitations in measuring LPF. The IPO seems to be prone to state effects, although correlations with PDs remained significant when controlling for clinical distress. The DRS seemed to be more independent from clinical distress but was unexpectedly unrelated to features of personality pathology. DRS reflects availability, while IPO also reflects different degrees of accessibility of LPF in PDs.  相似文献   
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With the emerging interest in regenerative medicine and tissue engineering, new treatment modalities being developed for joint disorders including joint surface lesions and articular cartilage defects. The clinical outcome of these novel approaches appears rather unpredictable and is due to many reasons but definitely also linked to the patient profile. As a typical example, symptomatic articular cartilage lesions can be presented in an otherwise normal joint, or associated with several other joint tissue alterations including meniscal lesions and abnormalities of the underlying bone. The outcome of novel treatments may well be influenced by the status of the whole joint, and the potential to develop osteoarthritis. To better identify the patients at risk and responders to certain treatments, it is of use to define and most importantly classify patients with “early osteoarthritis”. Here, classification criteria for this group of patients are presented, allowing a more defined and accurate inclusion in clinical trials in the future.  相似文献   
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OBJECTIVE: To study activation of intracellular pathways depending on nuclear factor kappa B (NFkappaB) and mitogen activated kinases (MAPK) in the synovium of patients with psoriatic arthritis before and after treatment with etanercept. METHODS: Synovial biopsies were obtained by needle arthroscopy of the knee in 9 patients with active psoriatic arthritis before the initiation of etanercept. Follow-up biopsies were taken in the same knee after 6 months. Synovitis was studied by histology. Pathway activation was studied by immunofluorescense for phosphorylated ERK, phosphorylated p38, phosphorylated JNK or phosphorylated inhibitor of kappa B (IkappaBalpha) using digital image analysis. RESULTS: Histological severity scores were significantly reduced after etanercept treatment. Activation of NFkappaB signaling was found in the lining layer, and in infiltrating and peri-vascular cells in the sublining zone. Activated p38 was present in both lining and sublining layer. In the sublining layer, positive cells were found in inflammatory infiltrates, in perivascular zones and in the endothelium. Activated ERK was mainly present in the sublining layer, both in mononuclear cell infiltrates and perivascularly. Occasional positive cells were found in the lining layer. Activation of JNK was recognized in cells of the lining layer, in some of the sublining cell infiltrates and the perivascular compartment. CONCLUSIONS: Etanercept therapy resulted in a significant decrease in NFkappaB, JNK and ERK, but not in p38 activation. Persistent activation of these pathways, albeit reduced, may trigger positive feedback loops and flares of arthritis after cessation of etanercept.  相似文献   
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ObjectivesThe standard framework of economic evaluation of health programs, which is increasingly used for policy funding decisions, is insufficiently equipped to reflect the full range of health and economic benefits conferred by vaccines and thus undervalues vaccination.MethodsIn 2019, a group of Belgian health economic and clinical experts, supported by 2 senior international vaccination experts (1 American, 1 Belgian), convened 4 roundtable meetings to highlight which particular value elements of vaccination remain neglected in economic evaluations.ResultsThey concluded that the standard economic evaluation framework fails to reflect the full value of vaccination with respect to prevention of complications linked to some vaccine-preventable diseases, health gains for caregivers, herd effects, changes in exposure to and distribution of serotypes, the effect on antimicrobial resistance, productivity gains for caregivers and patients, and the distributive implications of vaccination programs.ConclusionsHere, suggestions are made regarding how these shortcomings can be addressed in future economic evaluations of vaccines and how a more level playing field between vaccines and other health programs can be created.  相似文献   
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