178 research outputs found

    Cartilage and bone regeneration: how close are we to bedside?

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    The treatment/regeneration of bone and cartilage diseases or defects, whether induced by rheumatism, joint dysplasia, trauma, or surgery presents great challenges that have not been fully solved by the current therapies. In the last few years, tissue engineering and regenerative medicine have been proposing advanced tools and technologies for bone and cartilage tissue regeneration, and some of which have successfully reached the market. Beyond the source of cells, the creation of superior structures for replacing defective bone and cartilage requires strong research in biomechanical signaling and synthesis of advanced biomaterials to mimic human tissues at the most varied levels. Natural and synthetic polymers, bioresorbable inorganic materials, and composites have been investigated for its potential as scaffolding materials with enhanced mechanical and biological properties. Porous scaffolds, hydrogels, and fibers are the most commonly biomimetic structures used for bone and cartilage tissue engineering. Herein, the concepts and current treatment strategies for bone and cartilage repair, as well as biomimetic strategies for bone and cartilage tissue engineering are overviewed. A global review of the ongoing clinical trials and of the scaffolds commercially available for the repair of osteochondral tissue is also presented.(undefined

    Retrospective study of canine cutaneous tumors submitted to a diagnostic pathology laboratory in Northern Portugal (2014-2020)

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    Background Cutaneous neoplastic diseases are the most and second-most frequently reported tumors in male and female dogs, respectively. The aims of this study were to report the occurrence of canine cutaneous tumors in a pathology laboratory located in Northern Portugal between 2014 and 2020, and to characterize and categorize the anatomical locations, breed, age, and sex of the animals affected with different types of neoplasms. Results Throughout the 7-year study, 1,185 cases were diagnosed as cutaneous tumors, with 62.9% being classified as benign, and 37.1% as malignant. Mast cell tumors (22.7%) were the most frequently diagnosed tumor type, followed by benign soft tissue tumors (9.7%), sebaceous gland tumors (8.1%), vascular tumors (7.9%) and soft tissue sarcomas (7.6%). Cutaneous tumors commonly exhibited multicentric occurrence (14.6%) followed by single occurrence in hindlimb (12.1%), forelimb (8.6%), buttock (7.1%), abdominal (6.5%) and costal (5.2%) areas. The odds of developing cutaneous neoplasia were higher with increasing age (p < 0.001). Females had an increased odds of developing skin tumors compared to males (crude OR = 2.99, 95% (2.51, 3.55); adj OR = 2.93, 95% (2.46, 3.49). Purebred dogs, as a group, showed a reduced odds of developing cutaneous tumors when compared to mixed-breed dogs (crude OR = 0.63, 95% (0.53, 0.74); adj OR = 0.75, 95% (0.62, 0.89). Conclusions Mast cell tumors, benign soft tissue tumors and sebaceous tumors were the most common histotypes encountered. The epidemiological survey achieved with this study demonstrates the relative frequency of different types of tumors in this particular population. Furthermore, the results herein achieved can act as a basis or a beneficial reference for local veterinarians helping in the establishment of a preliminary and presumptive diagnosis of canine cutaneous tumors histotypes

    Novel bilayered Gellan gum/Gellan gum hydroxyapatite scaffolds for osteochondral tissue engineering applications

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    Osteoarthritis is a major cause of disability during aging. By the age of 60, close to 100% of the population will have histologic changes of degeneration in their knee cartilage (Loeser, 2000). Because of its avascular nature, cartilage has little capacity to self-regenerate. Despite the progress already achieved in osteochondral regeneration, some limitations have to be overcome. The formation of fibrocartilage has to be avoided and the innervation has to be improved. Further, one main feature to be promoted is the induction of vascularization in the bony part but not in the cartilage part and to avoid de-differentiation processes. A promising strategy could pass through the development and optimization of novel culture systems. The ideal approach could integrate scaffolds presenting regions with different physical characteristics, combined with different growth factors to support different stem cells fates, regarding the complex tissue physiology to be regenerate. This work aims to develop novel bilayered gellan gum (GG)/gellan gumhydroxyapatite (HAp) hydrogels based structures for osteochondral tissue engineering applications. Bilayered GG/GG-HAp hydrogels were produced by joining both solutions of GG 2% (w/v) with and without HAp (20% wt.) for bony and cartilage parts, respectively. The solutions were introduced into a silicone mould with 20:10 mm (height and diameter, respectively). Gelation of GG was promoted by immersion in PBS solution for 24 h. The architecture of the bilayered scaffolds was investigated by micro-computed tomography. Results have shown that the freeze-dried bilayered scaffolds composed by low acyl GG(2%(w/ v)/low acyl GG(2%(w/v)-HAp20%(w/w) possess a porosity of 83.4 ± 0.8%, pore size of 279.3 ± 38.6 lm and interconnectivity of 62.2 ± 5.4%. Degradability assays are being performed with the intent to use this system to culture human adipose derived stem cells inducing cell co-differentiation into chondrocytes and osteoblasts. Ultimately, the developed bilayered scaffolds will provide new therapeutic possibilities for the regeneration of osteochondral defects

    Gellan gum-based hydrogel bilayered scaffolds for osteochondral tissue engineering

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    It has been shown that hydrogel bilayered scaffolds combining cartilage- and bone-like layers are most advantageous for treating osteochondral defects. In this study, it is proposed the use of low acyl gellan gum (LAGG) for developing bilayered hydrogel scaffolds for osteochondral tissue engineering. The cartilage-like layer of the GG-based bilayered hydrogel scaffolds is composed of LAGG (2 wt%). By adding a 2 wt% LAGG aqueous solution to different amounts of HAp (5-20 wt%) it was possible to produce the bone-like layer. In vitro bioactivity tests were performed by means of soaking the LAGG/LAGG-HAp hydrogel scaffolds in a simulated body fluid solution up to 14 days. Scanning electron microscopy, Fourier transform infra-red spectroscopy and X-ray diffraction analyses demonstrated that apatite formation is limited to the bone-like layer of the LAGG/LAGG-HAp bilayered hydrogel scaffolds

    A short review of the distribution of short-beaked common dolphins (Delphinus delphis) in the central and eastern North Atlantic with an abundance estimate for part of this area

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    This paper uses data from 3 programmes: (1) the North Atlantic Sightings Surveys (NASS) surveys undertaken throughout much of the central and eastern North Atlantic north of about 40° N in 1987, 1989, 1995 and 2001; (2) the MICA-93 programme; and (3) the north eastern Atlantic segment of the Small Cetacean Abundance in the North Sea (SCANS) survey in 1994. The data from all surveys were used to examine the distribution of common dolphins in the NE Atlantic. No sightings were made north of 57° N. An initial attempt to examine distribution against 4 potential non biological explanatory variables was made. A simple interpretation of the preliminary analyses presented here is that the primary areas for groups of common dolphins were in waters over 15° C and depths of 400-1,000 m (there does appear a link with shelf features), between around 49°-55° N especially between 20°-30°W. An illustrative example of spatial modelling is presented. Only for 1 year (and part of the total survey area) were there sufficient data to attempt to estimate abundance: 1995. The estimated abundance in the W Block of the NASS-95 Faroese survey was 273,159 (cv=0.26; 95% CI=153,392-435,104) short-beaked common dolphins. This estimate is corrected for animals missed on the trackline (g(0)) and for responsive movement.Publisher PDFPeer reviewe

    3DICE coding matrix multidirectional macro-architecture modulates cell organization, shape, and co-cultures endothelization network

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    Natural extracellular matrix governs cells providing biomechanical and biofunctional outstanding properties, despite being porous and mostly made of soft materials. Among organs, specific tissues present specialized macro-architectures. For instance, hepatic lobules present radial organization, while vascular sinusoids are branched from vertical veins, providing specific biofunctional features. Therefore, it is imperative to mimic such structures while modeling tissues. So far, there is limited capability of coupling oriented macro-structures with interconnected micro-channels in programmable long-range vertical and radial sequential orientations. Herein, a three-directional ice crystal elongation (3DICE) system is presented to code geometries in cryogels. Using 3DICE, guided ice crystals growth templates vertical and radial pores through bulky cryogels. Translucent isotropic and anisotropic architectures of radial or vertical pores are fabricated with tunable mechanical response. Furthermore, 3D combinations of vertical and radial pore orientations are coded at the centimeter scale. Cell morphological response to macro-architectures is demonstrated. The formation of endothelial segments, CYP450 activity, and osteopontin expression, as liver fibrosis biomarkers, present direct response and specific cellular organization within radial, linear, and random architectures. These results unlock the potential of ice-templating demonstrating the relevance of macro-architectures to model tissues, and broad possibilities for drug testing, tissue engineering, and regenerative medicine.The authors are grateful for the Portuguese Foundation for Science and Technology (FCT) distinction attributed to R. F. Canadas (SFRH/ BD/92565/2013), and to J. M. Oliveira (IF/00423/2012, IF/01285/ 2015). R. F. Canadas is also thankful to FCT, Fundo Europeu de Desenvolvimento Regional (FEDER), and Programa Operacional Competitividade e Internacionalizaç˜ao (POCI) for funding the B-Liver Project (PTDC/EMD-EMD/29139/2017). The authors are also thankful to FCT for supporting the project Hierarchitech (M-ERA-NET/0001/2014) and for the funds provided under the 3 BioMeD project (JICAM/0001/2017). The authors acknowledge that this material and collaboration is based in part upon work supported by Luso-American Development Foundation (FLAD), 2016/CON15/CAN6). U. Demirci is also grateful for the Canary Center at Stanford for Cancer Early Detection Seed Award. The authors are also grateful for the support provided by Diana Bicho and Nicolas Cristini on scaffold characterization and cell culture, respectively

    Evaluation of alternative strategies to treat anoestrous dairy cows and implications for reproductive performance in pasture-based seasonal calving herds: A pilot study

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    peer-reviewedThe objective of the present study was to assess the effects on ovulation and reproductive performance of a single injection of either GnRH or hCG applied 9 days before the start of the seasonal breeding period in anovulatory anoestrus cows compared with a 7-day progesterone-Ovsynch protocol. The study was conducted on four grass-based seasonal calving dairy herds in Ireland. The total number of cows in the herds was 2112, of which 488 were diagnosed as anoestrus based on absence of behavioural oestrus during a 30 day period. Ovarian structures and the uterus were examined by transrectal ultrasound on all 488 presumptive anestrus cows 9 days before mating start date (MSD). The number of corpora lutea (CL), number of large follicles (≥10 mm) and uterine reproductive tract score were recorded. Only cows that had no CL, ultrasound reproductive tract score ≤2 and were ≥30 days in milk (DIM) were enrolled in the study (n = 214). Cows were blocked by parity, DIM and body condition score and randomly assigned to one of four treatments: i.m. injection of gonadotropin releasing hormone analogue [GnRH; (n = 57)], i.m. injection of human chorionic gonadotropin [hCG; (n = 48)], 7-day Progesterone-Ovsynch protocol [P4OV; (n = 60)] and Control (no hormonal intervention, n = 49). A second ultrasound examination was performed 7 days after treatment to determine ovulatory response. There was a treatment effect on ovulation rate (P < 0.0001), whereby Control cows had a lesser ovulation rate compared with GnRH-, hCG- and P4OV-treated cows. Submission rate during the first 21 days of the breeding period [SR21; (P = 0.74)], pregnant to first service [P/AI1; (P = 0.24)], pregnant within 42 days after the onset of breeding [P42; (P = 0.73)], and pregnant within 84 days after the onset of breeding were not affected by treatment. A tendency was observed (P = 0.07) for greater likelihood of pregnancy within 21 days after the onset of breeding (P21) for P4OV and Control cows compared with GnRH- and hCG-treated cows. GnRH- and hCG-treated cows tended (P = 0.10) to have greater P/AI1 when first service events occurred after day 21 of the breeding period compared with Control cows. P4OV cows had shorter MSD to first service interval (P = 0.0001) and shorter MSD to conception interval (P = 0.02) compared with Control, GnRH- and hCG-treated cows. In conclusion, treatment of anestrous cows with GnRH or hCG resulted in an increase in ovulation rate compared with untreated Control cows, but did not improve reproductive performance during the first 21 days of the breeding season. The best reproductive performance results were obtained with the P4OV treatment, but this treatment has the greatest cost, and has the greatest number of interventions. The observation of good P/AI1 in hCG- and GnRH- treated cows when the first insemination occurred later than day 21 after MSD warrants further investigation, and suggests that these interventions should be applied earlier than 9 days before the farm MSD

    Validation of a small-animal PET simulation using GAMOS: a Geant4-based framework

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    onte Carlo-based modelling is a powerful tool to help in the design and optimization of positron emission tomography (PET) systems. The performance of these systems depends on several parameters, such as detector physical characteristics, shielding or electronics, whose effects can be studied on the basis of realistic simulated data. The aim of this paper is to validate a comprehensive study of the Raytest ClearPET small-animal PET scanner using a new Monte Carlo simulation platform which has been developed at CIEMAT (Madrid, Spain), called GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations). This toolkit, based on the GEANT4 code, was originally designed to cover multiple applications in the field of medical physics from radiotherapy to nuclear medicine, but has since been applied by some of its users in other fields of physics, such as neutron shielding, space physics, high energy physics, etc. Our simulation model includes the relevant characteristics of the ClearPET system, namely, the double layer of scintillator crystals in phoswich configuration, the rotating gantry, the presence of intrinsic radioactivity in the crystals or the storage of single events for an off-line coincidence sorting. Simulated results are contrasted with experimental acquisitions including studies of spatial resolution, sensitivity, scatter fraction and count rates in accordance with the National Electrical Manufacturers Association (NEMA) NU 4-2008 protocol. Spatial resolution results showed a discrepancy between simulated and measured values equal to 8.4% (with a maximum FWHM difference over all measurement directions of 0.5 mm). Sensitivity results differ less than 1% for a 250–750 keV energy window. Simulated and measured count rates agree well within a wide range of activities, including under electronic saturation of the system (the measured peak of total coincidences, for the mouse-sized phantom, was 250.8 kcps reached at 0.95 MBq mL−1 and the simulated peak was 247.1 kcps at 0.87 MBq mL−1). Agreement better than 3% was obtained in the scatter fraction comparison study. We also measured and simulated a mini-Derenzo phantom obtaining images with similar quality using iterative reconstruction methods. We concluded that the overall performance of the simulation showed good agreement with the measured results and validates the GAMOS package for PET applications. Furthermore, its ease of use and flexibility recommends it as an excellent tool to optimize design features or image reconstruction techniques

    Associations between postpartum fertility phenotypes and genetic traits in seasonal-calving, pasture-based lactating dairy cows

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    peer-reviewedThe objective of this study was to evaluate the associations between corpus luteum (CL) status, uterine health, body condition score (BCS), metabolic status, and parity at wk 3 and 7 postpartum in seasonal-calving, pasture-based, lactating dairy cows. The associations between those phenotypes and individual genetic traits were also evaluated. First- and second-parity spring-calving lactating dairy cows (n = 2,600) from 35 dairy farms in Ireland were enrolled. Farms were visited every 2 weeks; cows that were at wk 3 (range 14 to 27 DIM) and wk 7 (range 42 to 55 DIM) postpartum were examined. Body condition score was measured using a scale of 1 to 5 with 0.25 increments. Transrectal ultrasound examination was performed at wk 3 and 7 postpartum to determine presence or absence of CL and ultrasound reproductive tract score. Blood samples were collected at each visit and the concentrations of glucose, β-hydroxybutyrate (BHB), and fatty acids (FA) were analyzed by using enzymatic colorimetry. Cows were grouped into 3 BCS categories [low (≤2.5), target (≥2.75 and ≤3.25), and high (≥3.5)]; 2 CL status categories: (present or absent); 2 uterine health status (UHS) categories (normal and abnormal); and 3 metabolic status categories [good (high glucose, low fatty acids and BHB), poor (low glucose, high fatty acids and BHB), and moderate (all other combinations)]. Fisher's exact test was used to test associations between variables and was supplemented by logistic regression. We found associations between UHS (wk 3 and 7), BCS (wk 3 and 7), parity (wk 3 and 7) metabolic status (wk 3), and predicted transmitting ability for calving interval (PTA for CIV; wk 3) and CL status. Cows that had abnormal UHS, low BCS, primiparity, and poor metabolic status, and were in the quartile with the greatest PTA for CIV were less likely to have had CL present at wk 3 and 7 postpartum. We also found associations between CL status (wk 3 and 7), BCS (wk 3 and 7), parity (wk 3 and 7), and PTA for CIV (wk 3) and UHS. Cows that did not have a CL present had low BCS, primiparity, and that were in the quartile with greatest PTA for CIV, had a greater risk of abnormal UHS at wk 3 and 7 postpartum. We observed strong associations between CL status, UHS, BCS, metabolic status, parity, and individual genetic traits at wk 3 and 7 postpartum in seasonal-calving, pasture-based lactating dairy cows. Achieving target BCS and good metabolic status, and selecting cows based on PTA for CIV, are all expected to increase the likelihood of hastening the resumption of estrous cyclicity and enhancing uterine health during the postpartum period
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