Comparison of two doses of bio-optimized Curcuma longa extract (BCL) in the management of symptomatic knee osteoarthritis (OA).
A prospective, randomized, 3-month, double-blind, multicenter, ...three-group, placebo-controlled trial assessing Patient Global Assessment of Disease Activity (PGADA) and serum sColl2-1, a biomarker of cartilage degradation, as co-primary endpoints. Pain on visual analog scale (VAS), Knee injury and Osteoarthritis Outcome Score (KOOS), and paracetamol/non-steroidal anti-inflammatory drug (NSAID) consumption were used as secondary endpoints.
One hundred fifty patients with knee OA were followed for 90 days. Low and high doses of BCL showed a greater decrease of PGADA than placebo. Analysis of sColl2-1 showed in the placebo and BCL low-dose groups, but not in the BCL high-dose group, a transient but non-significant increase of sColl2-1 between T0 and T1. Thereafter, in all groups, sColl2-1 decreased between T1 and T3 (all p < 0.01), but no difference between the groups was found. Pain reduction at day 90 in the low- and high-dose BCL groups (- 29.5 mm and - 36.5 mm) was higher than that in the placebo (- 8 mm; p = 0.018). The global KOOS significantly decreased overtime, but changes were comparable across treatment arms. The ratio of patients with adverse events (AE) related to the product was similar in the placebo and treatment groups, but the number of AE linked to the product was higher in the high-dose BCL group compared to the placebo (p = 0.012).
BCL appeared safe and well-tolerated with no evidence of severe adverse effects. Efficacy analysis suggested positive trends for measurements of PGADA and serum levels of an OA biomarker and showed a rapid and significant decrease of pain in knee OA (Trial registration: ISRCTN, ISRCTN12345678. Registered 21 September 2016-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02909621?term=osteoarthritis+curcumin&rank=5-Evaluation of FLEXOFYTOL® Versus PLACEBO (COPRA) NCT02909621).
Selective laser melting (SLM) is used to manufacture dense NiTi parts. The microstructure and texture are assessed (before and after annealing followed by furnace cooling) and linked to the ...compression behaviour and shape memory response. It is shown that SLM strongly orients the fine austenite subgrains towards the building direction. This texture induces the highest spring back along the building (vertical) direction and the lowest along the horizontal direction after compression. The compressive stiffness, on the other hand, is the highest along horizontal direction and the lowest in vertical direction. The internal stresses due to SLM processing are another factor that may induce large martensite plates, decreasing the spring back. Although post-annealing (followed by furnace cooling) annihilates these large SLM stress-induced martensite plates, it is unsuccessful to achieve completely isotropic properties. The furnace cooling after annealing may even segregate austenite and martensite within SLM solidified tracks, causing a mixed shape memory response.
Purpose
To develop a high‐resolution three‐dimensional (3D) magnetic resonance imaging (MRI)‐based treatment planning approach for uveal melanomas (UM) in proton therapy.
Materials/methods
For eight ...patients with UM, a segmentation of the gross tumor volume (GTV) and organs‐at‐risk (OARs) was performed on T1‐ and T2‐weighted 7 Tesla MRI image data to reconstruct the patient MR‐eye. An extended contour was defined with a 2.5‐mm isotropic margin derived from the GTV. A broad beam algorithm, which we have called πDose, was implemented to calculate relative proton absorbed doses to the ipsilateral OARs. Clinically favorable gazing angles of the treated eye were assessed by calculating a global weighted‐sum objective function, which set penalties for OARs and extreme gazing angles. An optimizer, which we have named OPT’im‐Eye‐Tool, was developed to tune the parameters of the functions for sparing critical‐OARs.
Results
In total, 441 gazing angles were simulated for every patient. Target coverage including margins was achieved in all the cases (V95% > 95%). Over the whole gazing angles solutions space, maximum dose (Dmax) to the optic nerve and the macula, and mean doses (Dmean) to the lens, the ciliary body and the sclera were calculated. A forward optimization was applied by OPT’im‐Eye‐Tool in three different prioritizations: iso‐weighted, optic nerve prioritized, and macula prioritized. In each, the function values were depicted in a selection tool to select the optimal gazing angle(s). For example, patient 4 had a T2 equatorial tumor. The optimization applied for the straight gazing angle resulted in objective function values of 0.46 (iso‐weighted situation), 0.90 (optic nerve prioritization) and 0.08 (macula prioritization) demonstrating the impact of that angle in different clinical approaches.
Conclusions
The feasibility and suitability of a 3D MRI‐based treatment planning approach have been successfully tested on a cohort of eight patients diagnosed with UM. Moreover, a gaze‐angle trade‐off dose optimization with respect to OARs sparing has been developed. Further validation of the whole treatment process is the next step in the goal to achieve both a non‐invasive and a personalized proton therapy treatment.
The growing interest for Selective Laser Melting (SLM) in orthopedic implant manufacturing is accompanied by the introduction of novel Ti alloys, in particular β-Ti for their excellent corrosion ...resistance as well as favorable combination of high mechanical strength, fatigue resistance and relatively low elastic modulus. As part of the SLM process for producing quality β-Ti parts powder flowability is essential to achieve uniform thickness of powder layers. In this work the flowability of different gas atomized β-Ti, including NiTi, powders has been studied. Their rheological properties were compared to those of commercially available plasma-atomized Ti–6Al–4V powder using a newly developed semi-automatic experimental set-up. Not only the particle size, shape and size distribution of the powders display a large influence on the powder flowability but also particle surface properties such as roughness, chemical composition and the presence of liquid on the surface of the particles. It was found that plasma or gas atomization production techniques for SLM powder have a considerable effect on the particle topography. Among the powders studied regarding SLM applicability only rheological properties of the fine size fraction (25–45μm) of Ti–45Nb didn't conform to SLM processing requirements. To improve flowability of the Ti–45Nb powder it was annealed both in air and argon atmosphere at 600°C during 1h, resulting in an improved rheological behavior suitable for SLM processing.
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•3 novel experimental set-ups were used to study flowability of β-Ti and NiTi powders.•These set-ups prove their relevance for testing powders intended for SLM.•Low flowability of Ti–45Nb gas atomized powder didn't allow SLM processing.•Annealed Ti–45Nb powder showed improved rheological behavior suitable for SLM.•A minimum performance limit below which successful SLM is possible was defined.
Short-term psychodynamic psychotherapy (STPP) is frequently used to treat depression, but it is unclear which patients might benefit specifically. Individual participant data (IPD) meta-analyses can ...provide more precise effect estimates than conventional meta-analyses and identify patient-level moderators. This IPD meta-analysis examined the efficacy and moderators of STPP for depression compared to control conditions.
PubMed, PsycInfo, Embase, and Cochrane Library were searched September 1st, 2022, to identify randomized trials comparing STPP to control conditions for adults with depression. IPD were requested and analyzed using mixed-effects models.
IPD were obtained from 11 of the 13 (84.6%) studies identified (n = 771/837, 92.1%; mean age = 40.8, SD = 13.3; 79.3% female). STPP resulted in significantly lower depressive symptom levels than control conditions at post-treatment (d = −0.62, 95%CI −0.76, −0.47, p < .001). At post-treatment, STPP was more efficacious for participants with longer rather than shorter current depressive episode durations.
These results support the evidence base of STPP for depression and indicate episode duration as an effect modifier. This moderator finding, however, is observational and requires prospective validation in future large-scale trials.
•Short-term psychodynamic psychotherapy (STPP) is a treatment for depression.•STPP is superior to control conditions in decreasing depressive symptoms.•Depressive episode duration might moderate STPP outcome.
A fish scale-derived collagen matrix (FSCM) is proposed as an alternative for human donor corneal tissue. Light scatter and light transmission of the FSCM were measured and compared with human ...cornea, and its short-term biocompatibility was tested in a rat model.
light scatter was determined with a straylight measuring device, whereas light transmission was measured using a broadband absorption spectrometer. for evaluation of the biocompatibiliy, three approaches were used: the FSCM was implanted as an anterior lamellar keratoplasty (ALK), placed in an interlamellar corneal pocket (IL), and placed subconjunctivally (SC). Transparency, neovascularization, and epithelial damage were followed for 21 days. Morphology and cellular infiltration were assessed histologically.
The amount of scattered light was comparable to that seen in early cataract and the percentage of light transmission was similar to the transmission through the human cornea. Implantation of the FSCM as an ALK led to mild haziness only, not obscuring the pupil, despite the development of neovascularization around the sutures; IL placement led to a moderate haze, partly obscuring the pupil, and to (partial) melting of the anterior corneal lamella. The SC group exhibited local swelling and induration, which decreased over time. Histology showed a chronic inflammation varying from mild and moderate in the ALK and IL group, to severe in the SC group.
In spite of technical difficulties, it was feasible to use the FSCM for ALK, whereas IL placement led to melting of the anterior lamella. Further studies are necessary for better understanding of its immunogenicity. The light scatter and transmission data show that the first version of this FSCM is comparable to human cornea tissue in this respect.
Uveal melanoma (UM) with an inflammatory phenotype, characterized by infiltrating leukocytes and increased human leukocyte antigen (HLA) expression, carry an increased risk of death due to ...metastases. These tumors should be ideal for T-cell based therapies, yet it is not clear why prognostically-infaust tumors have a high HLA expression. We set out to determine whether the level of HLA molecules in UM is associated with other genetic factors, HLA transcriptional regulators, or microenvironmental factors.
28 enucleated UM were used to study HLA class I and II expression, and several regulators of HLA by immunohistochemistry, PCR microarray, qPCR and chromosome SNP-array. Fresh tumor samples of eight primary UM and four metastases were compared to their corresponding xenograft in SCID mice, using a PCR microarray and SNP array.
Increased expression levels of HLA class I and II showed no dosage effect of chromosome 6p, but, as expected, were associated with monosomy of chromosome 3. Increased HLA class I and II protein levels were positively associated with their gene expression and with raised levels of the peptide-loading gene TAP1, and HLA transcriptional regulators IRF1, IRF8, CIITA, and NLRC5, revealing a higher transcriptional activity in prognostically-bad tumors. Implantation of fresh human tumor samples into SCID mice led to a loss of infiltrating leukocytes, and to a decreased expression of HLA class I and II genes, and their regulators.
Our data provides evidence for a proper functioning HLA regulatory system in UM, offering a target for T-cell based therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gelcasting, a near net shape technique Gilissen, R; Erauw, J.P; Smolders, A ...
Materials in engineering,
08/2000, Letnik:
21, Številka:
4
Journal Article
Recenzirano
Gelcasting is a new ceramic forming technique getting worldwide attention. The process is based on the casting of a slurry, containing powder, water and water-soluble organic monomers. After casting ...the monomer, the mixture is then polymerised to form gelled parts. Drying, burning out and sintering complete the manufacturing route. The process is generic and can be used for a wide range of ceramic and metallic powders. It is a suitable technique for the fabrication of near net shape prototypes or small series using cheap moulds. In contrast with slipcasting, gelled parts are more homogeneous and have a much higher green strength. Gelcast parts contain only a few percent of organic components making binder removal much less critical compared to injection moulding. In this contribution, we describe our experience of the gelcasting of Al
2O
3 powders. Until now special attention was given to the preparation of slurries with a high Al
2O
3 load, to the gelation itself, catalytic or thermal, to the choice of mould materials, to the drying step and to green machining.
The present study evaluated an innovative technique for the manufacturing of low-dosed tablets. Tablets containing hydroxyapatite and a pore forming agent (50% (w/w) Avicel PH 200/20, 37.5% and 50% ...corn starch/37.5% sorbitol) were manufactured by direct compression followed by sintering. The influence of pore forming agent (type and concentration), sinter temperature and sinter time on tablet properties was investigated. Sintering (1250
°C) revealed tablets with an acceptable friability (<1%). Using 50% (w/w) Avicel PH 200 as pore forming agent resulted in tablets combining the highest porosity (50%) and the highest median pore diameter (5
μm). Aqueous drug solutions (metoprolol tartrate, riboflavin sodium phosphate) were spiked on the tablet surface. The maximum volume of drug solution absorbed was limited (2
×
100μl), revealing that these porous carriers were ideal for low dosed formulations. Drug release from the tablets was slow, independent of the drug. To accelerate drug release, tablets were manufactured using a modified gelcasting technique yielding tablets with a median pore size of 60 and 80
μm. Release from these tablets was drastically increased indicating that the permeability of the tablets was influenced by the pore size, shape and connectivity of the porous network. Changing and controlling these parameters made it possible to obtain drug delivery systems providing different drug delivery behaviour.
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