Viscoelastic properties of human and bovine articular cartilage : a comparison of frequency-dependent trends

Acknowledgments The authors would like to thank Spencer C. Barnes and Hamid Sadeghi for assistance during experimentation. We would also like to thank patients donating tissue and the surgeons collecting these. Funding The equipment used in this study was funded by Arthritis Research UK (Grant number H0671). We are grateful to Arthritis Research UK for the award of a PhD studentship to Anna A. Cederlund (Grant number 19971). Arthritis Research UK had no role in the design of the study and collection, analysis and interpretation of data and in writing the manuscript.Peer reviewedPublisher PD

Anàlisi de polimorfismes en el gen APOE en una població de malalts d'Alzheimer de Mallorca

Objectiu: Verificar l'associació entre l'al ·lel APOE4, el polimorfisme del promotor APOE -491 T/A i el desenvolupament de malaltia d'Al zheimer. Pacients i mètodes: S'analitza el genotip APOE i el genotip del polimorfisme -491 T/A del promotor del gen APOE mitjançant peR seguida de digestió amb un enzim de restricció, en 34 pacients de Mallorca afectats de probable Malaltia d'Al zheimer i en 57 conh·ols sans. Resultats: A la nosh·a població, la freqüència de l'al·lel APOE4 va ser significativament superior en els pacients respecte dels controls (p=O,02; OR: 2,55). També la freqüència del genotip -491 AA mosh ·à una diferencia estadísticament significativa respecte de la població conh·ol (p=O,026; OR: 3,5). Quan es va analitzar la presència conjunta d'ambdós polimorfismes es comprovà com la possessió de l'al·lel APOE4 en un context d'alt nivell de producció de la proteïna ApoE, tal com ve determinat pel polimorfisme -491 AA, s'associà al major risc de desenvolupar la malaltia d'Alzheimer (p=O,0039; OR:4.73). Conclusions: Tant l'al·lel APOE-4 com el polimorfisme -491 A i molt mes la seva presencia conjunta constitueixen un factor important en el desenvolupament de malaltia d'Alzheimer

La oxitocina en el tratamiento de los déficits sociales asociados a los trastornos del espectro autista

Introducción: La implicación de la oxitocina en la conducta social de animales y humanos ha llevado a estudiar los efectos de su administración en el comportamiento y cognición social de pacientes con trastornos del espectro autista (TEA). Objetivos: Revisar la investigación sobre el potencial terapéutico de la oxitocina en el tratamiento de los déficits sociales de la población con TEA y discutir las probables direcciones futuras de los estudios en este campo. Desarrollo. Diversos trabajos han relacionado la oxitocina con la fisiopatología de los TEA. La mayoría de los estudios que han administrado oxitocina, generalmente por vía intranasal (24 UI), ha observado mejoras significativas en el rendimiento social, sin detectar efectos secundarios destacables. No obstante, existen datos contradictorios debido a la heterogeneidad de las variables analizadas por los diferentes estudios, al uso de muestras heterogéneas y pequeñas o a la diferente duración de los tratamientos. Las limitaciones relacionadas con la falta de comprensión de los mecanismos de acción de la oxitocina y la diversidad sintomatológica de los TEA dificultan el establecimiento de este péptido como tratamiento de los pacientes autistas. Estudios recientes destacan la conveniencia de explorar el efecto de la combinación del tratamiento de oxitocina con programas conductuales de intervención en habilidades sociales, así como la potenciación de la secreción endógena de oxitocina. Conclusiones: Los efectos de la administración de oxitocina resultan prometedores en relación con el tratamiento de los déficits sociales en individuos con TEA. Estudios futuros deberían facilitar la comprensión de las vías de acción de la oxitocina y el establecimiento de pautas óptimas de tratamientoThe recent involvement of oxytocin in social behavior of animals and humans has motivated the study of its effects on the social behavior of individuals with autism spectrum disorders (ASD).To review the current state of oxytocin studies concerning its therapeutic potential in treating social deficits of the ASD population, and to establish likely future directions to be taken by the studies in this field.Some studies have linked oxytocin to the pathophysiology of autistic disorders. Most studies that have administered oxytocin (mainly with intranasal administration of 24 IU) to ASD subjects have shown significant improvements in their social performance with acceptable safety parameters. However, there is controversial data as the outcome measures are widely dispersed, the samples are reduced and heterogeneous, and the treatment durations are different. The limitations related to the lack of understanding of the oxytocin's action mechanisms and the symptomatic heterogeneity of ASD are hampering progress towards the establishment of oxytocin as a treatment of ASD patients. Recent studies suggest the investigation of the combination of the oxytocin treatment with social skills training, and the enhancement of endogenous secretion of oxytocin.The effects of oxytocin are promising regarding the treatment of social deficits in ASD individuals. Future studies should aim to facilitate understanding of the oxytocin's ways of action and to establish the optimal treatment regim

Feasibility Study of a Proton Irradiation Facility for Radiobiological Measurements at an 18 MeV Cyclotron

A feasibility study of an experimental setup for the irradiation of biological samples at the cyclotron facility installed at the National Centre of Accelerators (Seville, Spain) is presented. This cyclotron, which counts on an external beam line for interdisciplinary research purposes, produces an 18 MeV proton beam, which is suitable for the irradiation of mono-layer cultures for the measurement of proton cell damages and Relative Biological Effectiveness (RBE) at energies below the beam nominal value. Measurements of this kind are of interest for proton therapy, since the variation of proton RBE at the distal edge of the Bragg curve may have implications in clinical proton therapy treatments. In the following, the characteristics of the beam line and the solutions implemented for the irradiation of biological samples are described. When dealing with the irradiation of cell cultures, low beam intensities and broad homogeneous irradiation fields are required, in order to assure that all the cells receive the same dose with a suitable dose rate. At the cyclotron, these constraints have been achieved by completely defocusing the beam, intercepting the beam path with tungsten scattering foils and varying the exit-window-to-sample distance. The properties of the proton beam thus obtained have been analysed and compared with Monte Carlo simulations. The results of this comparison, as well as the experimental measurement of the lateral dose profiles expected at the position of samples are presented. Meaningful dose rates of about 2–3 Gy/min have been obtained. Homogeneous lateral dose profiles, with maximum deviations of 5%, have been measured at a distance of approximately 50 cm in air from the exit window, placing a tungsten scattering foil of 200 μm in the beam path

Analysis of hydration and subchondral bone density on the viscoelastic properties of bovine articular cartilage.

Funding JC is currently funded by an Engineering and Physical Sciences Research Council scholarship (EP/N509590/1). We are also grateful to Arthritis Research UK for the award of a PhD studentship to Anna A. Cederlund (Grant number 19971). The materials and testing equipment used in this study was funded by an Arthritis Research UK grant (H0671). The Engineering and Physical Sciences Research Council and Arthritis Research UK (now part of Versus Arthritis) had no role in the design of the study and collection, analysis and interpretation of data and in writing the manuscript.Peer reviewedPublisher PD

Rational design of mitochondria targeted thiabendazole-based Ir(III) biscyclometalated complexes for a multimodal photodynamic therapy of cancer

Despite their outstanding properties as potential photosensitizers for photodynamic therapy (PDT), Ir(III) biscyclometalated complexes need both further developments to overcome remaining limitations and in-depth investigations into their mechanisms of action to reach clinic application in the treatment of cancer. This work describes the synthesis of a family of Ir(III) complexes of general formula [Ir(C^N)2(N^N′ )]Cl (N^N′ = thiabendazole-based ligands; C^N = ppy (2-phenylpyridinate) (Series A), or dfppy (2-(2,4-difluorophenyl)pyridinate) (Series B)) and their evaluation as potential PDT agents. These complexes are partially soluble in water and exhibit cytotoxic activity in the absence of light irradiation versus several cancer cell lines. Furthermore, the cytotoxic activity of derivatives of Series A is enhanced upon irradiation, particularly for complexes [1a]Cl and [3a]Cl, which show phototoxicity indexes (PI) above 20. Endocytosis was established as the uptake mechanism for [1a]Cl and [3a]Cl in prostate cancer cells by flow cytometry. These derivatives mainly accumulate in the mitochondria as shown by colocalization confocal microscopy experiments. Presumably, [1a]Cl and [3a]Cl induce death on cancer cells under irradiation through apoptosis triggered by a multimodal mechanism of action, which likely involves damage over mitochondrial DNA and mitochondrial membrane depolarization. Both processes seem to be the result of photocatalytic oxidation processes.We acknowledge the financial support provided by the Spanish Ministerio de Ciencia, Innovacion ´ y Universidades (RTI2018-100709-BC21, RTI2018-100709-B-C22) and CTQ (QMC)-RED2018-102471-T), Junta de Castilla y Leon ´ (BU087G19), Junta de Comunidades de CastillaLa Mancha-FEDER (JCCM) (grant SBPLY/19/180501/000260) and UCLM-FEDER (grants 2019-GRIN-27183 and 2019-GRIN-27209). I. Echevarría wants to acknowledge his fellowship to both the European Social Fund and Consejería de Educacion ´ de la Junta de Castilla y Leon ´ (EDU/1100/2017). E. Zafon wants to acknowledge her predoctoral fellowship to the Generalitat de Catalunya (AGAUR; 2021 FI_B 01036). We are also indebted to Jacinto Delgado, Pilar Castroviejo and Marta Mansilla (PCT of the Universidad de Burgos) for technical support and Jos´e Vicente Cuevas Vicario for advice and support with theoretical calculations and Gabriel García-Herbosa for providing us access to CV equipment

Cardioprotective effect of the mitochondrial unfolded protein response during chronic pressure overload

Background The mitochondrial unfolded protein response (UPRmt) is activated when misfolded proteins accumulate within mitochondria and leads to increased expression of mitochondrial chaperones and proteases to maintain protein quality and mitochondrial function. Cardiac mitochondria are essential for contractile function and regulation of cell viability, while mitochondrial dysfunction characterizes heart failure. The role of the UPRmt in the heart is unclear. Objectives The purpose of this study was to: 1) identify conditions that activate the UPRmt in the heart; and 2) study the relationship among the UPRmt, mitochondrial function, and cardiac contractile function. Methods Cultured cardiac myocytes were subjected to different stresses in vitro. Mice were subjected to chronic pressure overload. Tissues and blood biomarkers were studied in patients with aortic stenosis. Results Diverse neurohumoral or mitochondrial stresses transiently induced the UPRmt in cultured cardiomyocytes. The UPRmt was also induced in the hearts of mice subjected to chronic hemodynamic overload. Boosting the UPRmt with nicotinamide riboside (which augments NAD+ pools) in cardiomyocytes in vitro or hearts in vivo significantly mitigated the reductions in mitochondrial oxygen consumption induced by these stresses. In mice subjected to pressure overload, nicotinamide riboside reduced cardiomyocyte death and contractile dysfunction. Myocardial tissue from patients with aortic stenosis also showed evidence of UPRmt activation, which correlated with reduced tissue cardiomyocyte death and fibrosis and lower plasma levels of biomarkers of cardiac damage (high-sensitivity troponin T) and dysfunction (N-terminal pro–B-type natriuretic peptide). Conclusions These results identify the induction of the UPRmt in the mammalian (including human) heart exposed to pathological stresses. Enhancement of the UPRmt ameliorates mitochondrial and contractile dysfunction, suggesting that it may serve an important protective role in the stressed heart

JASON-1 CALVAL experiences in Cape of Begur and Ibiza island

The direct and indirect calibration experiences made at the Cape of Begur area in 1999, 2000 and 2002, for Topex/Poseidon and at the Ibiza island in 2003 have contributed to the international campaigns made at Harvest (USA), Corsica (France) and Bass (Australia). The main objective of IBIZA 2003 campaign has been the determination of the instantaneous sea surface/marine geoid gradient along Jason-1 tracks using a GPS catamaran and a network of GPS located in Portinatx and Ibiza and San Antonio harbours. The marine geoid will be used to relate the tide gauge coastal data with the altimeter data. We present the first results obtained with static and kinematic analysis of the data using different softwares.Peer ReviewedPostprint (published version

Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog

A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed

Mass fluxes, biogeochemistry and currents: Components for dynamics of particle fluxes in the Blanes submarine canyon (Northwestern Mediterranean)

XV Seminario Ibérico de Química Marina, Vigo, 22-24 de febrero de 2010N