Purpose
To study the influence of scaffold properties on the organization of in vivo cartilage regeneration. Our hypothesis was that stress transmission to the cells seeded inside the pores of the ...scaffold or surrounding it, which is highly dependent on the scaffold properties, determines the differentiation of both mesenchymal cells and dedifferentiated autologous chondrocytes.
Methods
4 series of porous scaffolds made of different polyacrylate polymers, previously seeded with cultured rabbit chondrocytes or without cells, were implanted in cartilage defects in rabbits. Subchondral bone was injured during the surgery to allow blood to reach the implantation site and fill the scaffold pores.
Results
At 3 months after implantation, excellent tissue regeneration was obtained, with a well-organized layer of hyaline-like cartilage at the condylar surface in most cases of the hydrophobic or slightly hydrophilic series. The most hydrophilic material induced the poorest regeneration. However, no statistically significant difference was observed between preseeded and non-preseeded scaffolds. All of the materials used were biocompatible, biostable polymers, so, in contrast to some other studies, our results were not perturbed by possible effects attributable to material degradation products or to the loss of scaffold mechanical properties over time due to degradation.
Conclusions
Cartilage regeneration depends mainly on the properties of the scaffold, such as stiffness and hydrophilicity, whereas little difference was observed between preseeded and non-preseeded scaffolds.
Purpose Androgen deprivation therapy may promote the development of the metabolic syndrome in patients with prostate cancer. We assessed the prevalence of the full metabolic syndrome and its ...components during the first year of androgen deprivation therapy. Materials and Methods This observational, multicenter, prospective study included 539 patients with prostate cancer scheduled to receive 3-month depot luteinizing hormone-releasing hormone analogs for more than 12 months. Waist circumference, body mass index, lipid profile, blood pressure and fasting glucose were evaluated at baseline and after 6 and 12 months. The metabolic syndrome was assessed according to NCEP ATP III criteria (2001) and 4 other definitions (WHO 1998, AACE 2003, AHA/NHLBI 2005 and IDF 2005). Results At 6 and 12 months after the initiation of androgen deprivation therapy, significant increases were observed in waist circumference, body mass index, fasting glucose, triglycerides, total cholesterol, and high-density and low-density lipoprotein cholesterol. No significant changes in blood pressure 130/85 or greater were detected. A nonsignificant increase of 3.9% in the prevalence of the full metabolic syndrome (ATP III) was observed (22.9% at baseline vs 25.5% and 26.8% at 6 and 12 months, respectively). The prevalence of the metabolic syndrome at baseline varied according to the definition used, ranging from 9.4% (WHO) to 50% (IDF). At 12 months significant increases in prevalence were observed with the WHO (4.1%) and AHA/NHLBI (8.1%) definitions. Conclusions Androgen deprivation therapy produces significant early effects on waist circumference, body mass index, fasting glucose, triglycerides and cholesterol. The prevalence of and increase in the metabolic syndrome depend on the defining criteria. Counseling patients on the prevention, early detection and treatment of specific metabolic alterations is recommended.
The generation of pathogen-specific immune responses is dependent on the signaling capabilities of pathogen-recognition receptors. DC-SIGN is a C-type lectin that mediates capture and internalization ...of viral, bacterial, and fungal pathogens by myeloid dendritic cells. DC-SIGN–interacting pathogens are thought to modulate dendritic cell maturation by interfering with intracellular signaling from Toll-like receptor molecules. We report that engagement of DC-SIGN by specific antibodies does not promote dendritic cell maturation but induces ERK1/2 and Akt phosphorylation without concomitant p38MAPK activation. DC-SIGN ligation also triggers PLCγ phosphorylation and transient increases in intracellular calcium in dendritic cells. In agreement with its signaling capabilities, a fraction of DC-SIGN molecules partitions within lipid raft–enriched membrane fractions both in DC-SIGN–transfected and dendritic cells. Moreover, DC-SIGN in dendritic cells coprecipitates with the tyrosine kinases Lyn and Syk. The relevance of the DC-SIGN–initiated signals was demonstrated in monocyte-derived dendritic cells, as DC-SIGN cross-linking synergizes with TNF-α for IL-10 release and enhances the production of LPS-induced IL-10. These results demonstrate that DC-SIGN–triggered intracellular signals modulate dendritic cell maturation. Since pathogens stimulate Th2 responses via preferential activation of ERK1/2, these results provide a molecular explanation for the ability of DC-SIGN–interacting pathogens to preferentially evoke Th2-type immune responses.
Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model.
A full-depth chondral defect along with subchondral bone injury were originated in the knee ...joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation.
Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface.
Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.
Purpose
Articular cartilage has limited repair capacity. Two different implant devices for articular cartilage regeneration were tested in vivo in a sheep model to evaluate the effect of subchondral ...bone anchoring for tissue repair.
Methods
The implants were placed with press-fit technique in a cartilage defect after microfracture surgery in the femoral condyle of the knee joint of the sheep and histologic and mechanical evaluation was done 4.5 months later. The first group consisted of a biodegradable polycaprolactone (PCL) scaffold with double porosity. The second test group consisted of a PCL scaffold attached to a poly(L-lactic acid) (PLLA) pin anchored to the subchondral bone.
Results
For both groups most of the defects (75%) showed an articular surface that was completely or almost completely repaired with a neotissue. Nevertheless, the surface had a rougher appearance than controls and the repair tissue was immature. In the trials with solely scaffold implantation, severe subchondral bone alterations were seen with many large nodular formations. These alterations were ameliorated when implanting the scaffold with a subchondral bone anchoring pin.
Discussions
The results show that tissue repair is improved by implanting a PCL scaffold compared to solely microfracture surgery, and most importantly, that subchondral bone alterations, normally seen after microfracture surgery, were partially prevented when implanting the PCL scaffold with a fixation system to the subchondral bone.
The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis ...(LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ± 12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 1.81-3.22, P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0.001), and responded better to specific treatments for LN (P = 0.014). More than two-thirds of the patients with LN from a wide European cohort achieved a complete response to treatment. The presence of positive anti-Sm antibodies was associated with a higher frequency of LN and a decreased rate of complete response to treatment. The use of antimalarials reduced both the risk of developing renal disease and its severity, and contributed to attaining a complete renal response.
The segmentation of the heart is usually demanded in the clinical practice for computing functional parameters in patients, such as ejection fraction, cardiac output, peak ejection rate, or filling ...rate. Because of the time required, the manual delineation is typically limited to the left ventricle at the end-diastolic and end-systolic phases, which is insufficient for computing some of these parameters (e.g., peak ejection rate or filling rate). Common computer-aided (semi-)automated approaches for the segmentation task are computationally demanding, and an initialization step is frequently needed. This work is intended to address the aforementioned problems by providing an image-driven method for the accurate segmentation of the heart from computed tomography scans. The resulting algorithm is fast and fully automatic (even the region of interest is delimited without human intervention). The proposed methodology relies on image processing and analysis techniques (such as multi-thresholding based on statistical local and global parameters, mathematical morphology, and image filtering) and also on prior knowledge about the cardiac structures involved. Segmentation results are validated through the comparison with manually delineated ground truth, both qualitatively (no noticeable errors found after visual inspection) and quantitatively (mass overlapping over 90%).
On improving CNNs performance: The case of MNIST Alvear-Sandoval, Ricardo F.; Sancho-Gómez, José L.; Figueiras-Vidal, Aníbal R.
Information fusion,
December 2019, 2019-12-00, Letnik:
52
Journal Article
Recenzirano
•We check that CNNs accept performance improvement techniques in MNIST.•These techniques reduce the advantage of CNNs over SDAE classifiers.•Adding a SDAE classifier over an improved CNN ensemble ...improves results.•The above approaches provide MNIST classification records.•We indicate some research lines emerging from this work.
In this note, we follow two directions to improve the performance of CNN classifiers. The first is to apply to CNN units the same improvement techniques that we have successfully used with Stacked Denoising Auto-Encoder classifiers. This leads to obtain a new performance record when classifying MNIST digits. The second consists of applying a Stacked Denoising Auto-Encoder classifier to the output of the best of the previous designs, trying to take advantage of the limitations of CNN architectures. An even better classification record is obtained for MNIST.
The above results permit to conclude that combining improvement techniques and stacking deep machines of different nature can be useful to better solve other real-world problems.
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