Cannabidiol Enhances the Passage of Lipid Nanocapsules across the Blood–Brain Barrier Both in Vitro and in Vivo

Diseases affecting the central nervous system (CNS) should be regarded as a major health challenge due to the current lack of effective treatments given the hindrance to brain drug delivery imposed by the blood–brain barrier (BBB). Since efficient brain drug delivery should not solely rely on passive targeting, active targeting of nanomedicines into the CNS is being explored. The present study is devoted to the development of lipid nanocapsules (LNCs) decorated with nonpsychotropic cannabinoids as pioneering nonimmunogenic brain-targeting molecules and to the evaluation of their brain-targeting ability both in vitro and in vivo. Noticeably, both the permeability experiments across the hCMEC/D3 cell-based in vitro BBB model and the biodistribution experiments in mice consistently demonstrated that the highest brain-targeting ability was achieved with the smallest-sized cannabinoid-decorated LNCs. Importantly, the enhancement in brain targeting achieved with the conjugation of cannabidiol to LNCs outperformed by 6-fold the enhancement observed for the G-Technology (the main brain active strategy that has already entered clinical trials for the treatment of CNS diseases). As the transport efficiency across the BBB certainly determines the efficacy of the treatments for brain disorders, small cannabinoid-decorated LNCs represent auspicious platforms for the design and development of novel therapies for CNS diseases

SO(p,q)-Higgs bundles and Higher Teichmuller components

Some connected components of a moduli space are mundane in the sense that they are distinguished only by obvious topological invariants or have no special characteristics. Others are more alluring and unusual either because they are not detected by primary invariants, or because they have special geometric significance, or both. In this paper we describe new examples of such 'exotic' components in moduli spaces of of SO(p, q)-Higgs bundles on closed Riemann surfaces or, equivalently, moduli spaces of surface group representations into the Lie group SO(p, q). Furthermore, we discuss how these exotic components are related to the notion of positive Anosov representations recently developed by Guichard and Wienhard. We also provide a complete count of the connected components of these moduli spaces (except for SO(2, q), with q >= 4)

Traffic signs recognition for detailed digital maps development and driver assistance systems

Digital maps are considered as an additional sensor in many of the new ADAS, but these systems usually require a higher level of accuracy and detail of the maps. Among the important information that the maps should contain are the road geometry and traffic signs. In the first case, it is interesting to use accurate and fast methods for measurement. In the paper, a method based on a datalog vehicle is used. Satellite positioning and inertial measurements systems data are combined and dynamic behavior of the vehicle body is corrected measuring the movements of the suspension system. On the other hand, the information provided by traffic signs and route-guidance signs is extremely important for safe and successful driving. An automatic system that is capable of extracting and identifying these signs automatically would help human drivers enormously; navigation would be easier, allowing them to concentrate on driving the vehicle. A Computer Vision System is used to recognize and classify the different families of traffic signs combining it with GPS information to develop detailed and accurate digital maps. This sign recognition can also be used for real time warnings to the driver. Some results of test carried out in real situations are shown

Influence of age, gender and obesity on pressure discomfort threshold of the foot: A cross-sectional study

[EN] Background: Foot pain is a highly prevalent health problem for which measures such as a pattern of Pressure Discomfort Threshold of the foot plantar surface can provide valuable information for orthosis design. This study aimed to describe such pattern as a tool for the assessment of painful conditions of the feet and to analyse how it modifies according to age, gender and obesity. Methods: A cross-sectional study was performed with participants allocated in: Group 1 people aged 20 to 35 years, Group 2 aged 50 to 65 years and Group 3 aged over 65. Pressure Discomfort Threshold on twelve points of the foot plantar surface was measured with an adapted manual dynamometer. Inferential analyses of the data were performed using one-way analysis of variance (ANOVA) considering foot areas, age group, gender and obesity. Findings: 36 participants were analysed. The pattern of Pressure Discomfort Threshold for all individuals showed a significantly higher threshold on the heel and external foot (P < 0.001, eta(2) = 0.124) and was statistical significantly influenced by age (P < 0.001, eta(2) = 0.17), especially in participants aged over 65; by gender, with women having higher values (P < 0.001, eta(2) = 0.13), and by obesity (P < 0.001, eta(2) = 0.19). Interpretation: A Pressure Discomfort Threshold pattern exists in the foot plantar surface. The characteristics of the discomfort pattern of the foot and its association with aging, gender and obesity may have considerable implications for orthosis and footwear design.Dueñas, L.; Arnal-Gómez, A.; Aparicio, I.; Balasch-Bernat, M.; López-Bueno, L.; Gonzalez Garcia, JC.; Solves Camallonga, C.... (2021). Influence of age, gender and obesity on pressure discomfort threshold of the foot: A cross-sectional study. Clinical Biomechanics. 82(105252):1-7. https://doi.org/10.1016/j.clinbiomech.2020.105252S1782105252AKDEMIR, O., BILKAY, U., TIFTIKCIOGLU, Y. O., OZEK, C., YAN, H., ZHANG, F., & AKIN, Y. (2010). New alternative in treatment of callus. The Journal of Dermatology, 38(2), 146-150. doi:10.1111/j.1346-8138.2010.00978.xAnguera, J. A., & Gazzaley, A. (2012). Dissociation of motor and sensory inhibition processes in normal aging. Clinical Neurophysiology, 123(4), 730-740. doi:10.1016/j.clinph.2011.08.024Awale, A., Dufour, A. B., Katz, P., Menz, H. B., & Hannan, M. T. (2016). Link Between Foot Pain Severity and Prevalence of Depressive Symptoms. Arthritis Care & Research, 68(6), 871-876. doi:10.1002/acr.22779Bacarin, T. A., Sacco, I. C. N., & Hennig, E. M. (2009). Plantar pressure distribution patterns during gait in diabetic neuropathy patients with a history of foot ulcers. Clinics, 64(2). doi:10.1590/s1807-59322009000200008Barlow, A., Braid, S., & Jayson, M. (1990). Foot problems in the elderly. Clinical Rehabilitation, 4(3), 217-222. doi:10.1177/026921559000400306Betts, R. P., Franks, C. I., & Duckworth, T. (1980). Analysis of pressure and loads under the foot. II. Quantitation of the dynamic distribution. Clinical Physics and Physiological Measurement, 1(2), 113-124. doi:10.1088/0143-0815/1/2/002Bus, S. A., Ulbrecht, J. S., & Cavanagh, P. R. (2004). Pressure relief and load redistribution by custom-made insoles in diabetic patients with neuropathy and foot deformity. Clinical Biomechanics, 19(6), 629-638. doi:10.1016/j.clinbiomech.2004.02.010Caravaggi, P., Giangrande, A., Lullini, G., Padula, G., Berti, L., & Leardini, A. (2016). In shoe pressure measurements during different motor tasks while wearing safety shoes: The effect of custom made insoles vs. prefabricated and off-the-shelf. Gait & Posture, 50, 232-238. doi:10.1016/j.gaitpost.2016.09.013Duckworth, T., Boulton, A., Betts, R., Franks, C., & Ward, J. (1985). Plantar pressure measurements and the prevention of ulceration in the diabetic foot. The Journal of Bone and Joint Surgery. British volume, 67-B(1), 79-85. doi:10.1302/0301-620x.67b1.3968150Dufour, A. B., Broe, K. E., Nguyen, U.-S. D. T., Gagnon, D. R., Hillstrom, H. J., Walker, A. H., … Hannan, M. T. (2009). Foot pain: Is current or past shoewear a factor? Arthritis & Rheumatism, 61(10), 1352-1358. doi:10.1002/art.24733Von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., & Vandenbroucke, J. P. (2008). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Journal of Clinical Epidemiology, 61(4), 344-349. doi:10.1016/j.jclinepi.2007.11.008Fillingim, R. B. (2000). Sex, gender, and pain: Women and men really are different. Current Review of Pain, 4(1), 24-30. doi:10.1007/s11916-000-0006-6Gonzalez JC, García AC, Vivas MJ, Ferrús E, Alcántara E, Forner A. A new portable method for the measurement of pressure discomfort threshold on the foot plant. Fourth symposium of the Technical Group on Footwear Biomechanics. 5–7 August 1999. Canmore, Canada. International Society of Biomechanics.Gorter, K., Kuyvenhoven, M., & de Melker, R. (2000). Nontraumatic foot complaints in older people. A population-based survey of risk factors, mobility, and well-being. Journal of the American Podiatric Medical Association, 90(8), 397-402. doi:10.7547/87507315-90-8-397Greenspan, J. D., Craft, R. M., LeResche, L., Arendt-Nielsen, L., Berkley, K. J., Fillingim, R. B., … Traub, R. J. (2007). Studying sex and gender differences in pain and analgesia: A consensus report. Pain, 132(Supplement 1), S26-S45. doi:10.1016/j.pain.2007.10.014Hennig, E. M., & Sterzing, T. (2009). Sensitivity Mapping of the Human Foot: Thresholds at 30 Skin Locations. Foot & Ankle International, 30(10), 986-991. doi:10.3113/fai.2009.0986Hill, C. L., Gill, T. K., Menz, H. B., & Taylor, A. W. (2008). Prevalence and correlates of foot pain in a population-based study: the North West Adelaide health study. Journal of Foot and Ankle Research, 1(1). doi:10.1186/1757-1146-1-2Hills, A., Hennig, E., McDonald, M., & Bar-Or, O. (2001). Plantar pressure differences between obese and non-obese adults: a biomechanical analysis. International Journal of Obesity, 25(11), 1674-1679. doi:10.1038/sj.ijo.0801785Hong, W.-H., Lee, Y.-H., Chen, H.-C., Pei, Y.-C., & Wu, C.-Y. (2005). Influence of Heel Height and Shoe Insert on Comfort Perception and Biomechanical Performance of Young Female Adults During Walking. Foot & Ankle International, 26(12), 1042-1048. doi:10.1177/107110070502601208Le Johansson, L., Kjellberg, A., Kilbom, A., & Hagg, G. M. (1999). Perception of surface pressure applied to the hand. Ergonomics, 42(10), 1274-1282. doi:10.1080/001401399184947Kwan, R. L.-C., Zheng, Y.-P., & Cheing, G. L.-Y. (2010). The effect of aging on the biomechanical properties of plantar soft tissues. Clinical Biomechanics, 25(6), 601-605. doi:10.1016/j.clinbiomech.2010.04.003Machado, Á. S., Bombach, G. D., Duysens, J., & Carpes, F. P. (2016). Differences in foot sensitivity and plantar pressure between young adults and elderly. Archives of Gerontology and Geriatrics, 63, 67-71. doi:10.1016/j.archger.2015.11.005McPoil, T. G., & Cornwall, M. W. (2006). Plantar tactile sensory thresholds in healthy men and women. The Foot, 16(4), 192-197. doi:10.1016/j.foot.2006.07.001Messing, K., & Kilbom, Å. (2001). Standing and very slow walking: foot pain-pressure threshold, subjective pain experience and work activity. Applied Ergonomics, 32(1), 81-90. doi:10.1016/s0003-6870(00)00030-2Mickle, K. J., & Steele, J. R. (2015). Obese older adults suffer foot pain and foot-related functional limitation. Gait & Posture, 42(4), 442-447. doi:10.1016/j.gaitpost.2015.07.013Mickle, K. J., Munro, B. J., Lord, S. R., Menz, H. B., & Steele, J. R. (2010). Foot Pain, Plantar Pressures, and Falls in Older People: A Prospective Study. Journal of the American Geriatrics Society, 58(10), 1936-1940. doi:10.1111/j.1532-5415.2010.03061.xOkifuji, A., Bradshaw, D. H., & Olson, C. (2009). Evaluating obesity in fibromyalgia: neuroendocrine biomarkers, symptoms, and functions. Clinical Rheumatology, 28(4), 475-478. doi:10.1007/s10067-009-1094-2Redmond, A. C., Landorf, K. B., & Keenan, A.-M. (2009). Contoured, prefabricated foot orthoses demonstrate comparable mechanical properties to contoured, customised foot orthoses: a plantar pressure study. Journal of Foot and Ankle Research, 2(1). doi:10.1186/1757-1146-2-20Shrout, P. E., & Fleiss, J. L. (1979). Intraclass correlations: Uses in assessing rater reliability. Psychological Bulletin, 86(2), 420-428. doi:10.1037/0033-2909.86.2.420Veves, A., Murray, H. J., Young, M. J., & Boulton, A. J. M. (1992). The risk of foot ulceration in diabetic patients with high foot pressure: a prospective study. Diabetologia, 35(7), 660-663. doi:10.1007/bf00400259Weerasinghe, T. W., Goonetilleke, R. S., & Reischl, U. (2016). Pressure thresholds and stiffness on the plantar surface of the human foot. Ergonomics, 60(7), 985-996. doi:10.1080/00140139.2016.1229042Xiong, S., Goonetilleke, R. S., Witana, C. P., & Rodrigo, W. D. A. S. (2010). An indentation apparatus for evaluating discomfort and pain thresholds in conjunction with mechanical properties of foot tissue in vivo. The Journal of Rehabilitation Research and Development, 47(7), 629. doi:10.1682/jrrd.2009.09.0152Xiong, S., Goonetilleke, R. S., & Jiang, Z. (2011). Pressure thresholds of the human foot: measurement reliability and effects of stimulus characteristics. Ergonomics, 54(3), 282-293. doi:10.1080/00140139.2011.552736Xu, R., Wang, Z., Ma, T., Ren, Z., & Jin, H. (2019). Effect of 3D Printing Individualized Ankle-Foot Orthosis on Plantar Biomechanics and Pain in Patients with Plantar Fasciitis: A Randomized Controlled Trial. Medical Science Monitor, 25, 1392-1400. doi:10.12659/msm.915045Van der Zwaard, B. C., Elders, P. J., Knol, D. L., Gorter, K. J., Peeraer, L., van der Windt, D. A., & van der Horst, H. E. (2011). Treatment of forefoot problems in older people: study protocol for a randomised clinical trial comparing podiatric treatment to standardised shoe advice. Journal of Foot and Ankle Research, 4(1). doi:10.1186/1757-1146-4-1

Desarrollo de la colección de publicaciones periódicas en una biblioteca especializada o centro de documentación

The purpose of this paper is to study the basic serials for a specialised library, in this case in Life Science. The methods we made use of can be applied to serials in any subject and consisted in access, consult, comparison and analysis of the difTerent specialised databases, both in CD-ROM support and in printed or magnetic support. A list of indexed titles was extracted from these databases and a comparison, confrontation and analysis took place. Finally, the list of seríais obtained was compared with the Journal Citation Reports in arder to analyze the proximity of both lists.El objetivo de este trabajo es hacer una selección de las publicaciones periódicas básicas que una biblioteca especializada debe contener, en este caso en el área de Biomedicina. La metodología empleada es aplicable a publicaciones periódicas de cualquier campo temático y consistió en el acceso, consulta, comparación y análisis de las distintas bases de datos especializadas, tanto en soporte CD-ROM, como impreso o magnético. Se extrajo una lista de títulos indizados por estas bases de datos y se procedió a la comparación, confrontación y análisis de los títulos obtenidos. La selección de revistas obtenida se comparó con la del Journal Citation Reports para analizar en qué medida se aproximan ambos listados

Aplicación de modelos ecológicos para el análisis de la estructura y dinámica de bosques Ibéricos en respuesta al cambio climático

Los modelos son simplificaciones de la realidad, su uso en Ecolog&iacute;a permite estudiar patrones y procesos en sistemas naturales complejos de manera objetiva y relativamente sencilla. Los ecosistemas forestales son especialmente complejos de estudiar al estar formados por especies longevas y de gran tama&ntilde;o, donde la experimentaci&oacute;n es dif&iacute;cil. La combinaci&oacute;n de modelos y datos observacionales a escalas espaciales regionales y continentales es particularmente &uacute;til para analizar patrones y procesos en bosques. La distribuci&oacute;n y abundancia de organismos a lo largo del espacio y el tiempo est&aacute; determinada por factores ambientales, bi&oacute;ticos y antr&oacute;picos, como por ejemplo las condiciones clim&aacute;ticas, la competencia inter- e intra-espec&iacute;fica, la adaptaci&oacute;n local, la plasticidad fenot&iacute;pica o la gesti&oacute;n forestal. Por lo tanto, para el estudio de la respuesta de los bosques frente al cambio global es aconsejable el uso de modelos que incluyan estos factores de cambio y su efecto en los patrones y procesos observados. De hecho, el uso de modelos apropiadas a escalas regionales supone un paso fundamental para estimar los posibles impactos, la vulnerabilidad de los bosques y establecer prioridades en las estrategias de mitigaci&oacute;n y adaptaci&oacute;n al cambio clim&aacute;tico. En el presente cap&iacute;tulo presentamos brevemente las t&eacute;cnicas m&aacute;s utilizadas para la parametrizaci&oacute;n de modelos en Ecolog&iacute;a, y la aplicaci&oacute;n de ciertos modelos para analizar los impactos y la vulnerabilidad de los bosques frente al cambio global. Dentro de las aplicaciones, incluimos desde modelos estad&iacute;sticos correlacionales para analizar patrones (e.g. Modelos de Distribuci&oacute;n de Especies o modelos de procesos demogr&aacute;ficos) hasta modelos din&aacute;micos que incorporan procesos demogr&aacute;ficos para explicar patrones de distribuci&oacute;n. Finalmente, discutimos&nbsp; el uso de estos modelos como herramientas para el diagn&oacute;stico de los impactos del cambio clim&aacute;tico sobre los bosques Ib&eacute;ricos y su importancia para el dise&ntilde;o de estrategias de adaptaci&oacute;n

Trastuzumab and pertuzumab without chemotherapy in early-stage HER2+ breast cancer: a plain language summary of the PHERGain study

This is a summary of a publication about the PHERGain study, which was published in The Lancet Oncology in May 2021. The study includes 376 women with a type of breast cancer called HER2-positive breast cancer that can be removed by surgery. In the study, researchers wanted to learn if participants could be treated with two medicines called trastuzumab and pertuzumab without the need for chemotherapy. To identify HER2-positive tumors with more sensitivity to anti-HER2 therapies, the researchers used a type of imaging called a FDG-PET scan to check how well the treatments were working.Participants took a treatment before surgery, consisting of either chemotherapy (docetaxel and carboplatin) plus trastuzumab and pertuzumab (group A) or trastuzumab and pertuzumab alone (plus hormone therapy if the tumor was hormone receptor-positive; group B). After two cycles of treatment, participants underwent a FDG-PET scan. Participants assigned to group A completed 6 cycles of treatment regardless of 18F-FDG-PET results. Participants in group B continued the same treatment until surgery if their FDG-PET scan showed the treatment was working. While participants who did not show a response started treatment with chemotherapy in addition to trastuzumab and pertuzumab. All participants then had surgery.The results revealed that, of the participants in group B who showed a response using FDG-PET scan, 37.9% achieved a disappearance of all invasive cancer in the breast and axillary lymph nodes. This rate appears to be higher than those reported in previous studies evaluating the same treatment. These participants also had less side effects and improved overall quality of life compared with participants taking chemotherapy plus trastuzumab and pertuzumab.Early monitoring of how well participants respond to treatment by FDG-PET scan seems to identify participants with operable HER2-positive breast cancer who were more likely to benefit from trastuzumab and pertuzumab without the need to have chemotherapy. The PHERGain study is still ongoing and results on long-term survival are expected to be released in 2023. Clinical Trial Registration: NCT03161353 (ClinicalTrials.gov)

The Right to Code and Share Arms

Glycerol is, to date, the most widely used cryoprotectant to freeze stallion spermatozoa at concentrations between 2% and 5%. Cryoprotectant toxicity has been claimed to be the single most limiting factor for the success of cryopreservation. In order to evaluate the toxic effects of the concentrations of glycerol used in practice, stallion spermatozoa were incubated in Biggers Whitten and Whittingham (BWW) media supplemented with 0%, 0.5%, 1.5%, 2.5%, 3.5%, and 5% glycerol. In two additional experiments, a hyposmotic (75 mOsm/kg) and a hyperosmotic (900 mOsm/kg) control media were included. Sperm parameters evaluated included cell volume, membrane integrity, lipid peroxidation, caspase 3, 7, and 8 activation, mitochondrial membrane potential, and integrity of the cytoskeleton. Glycerol exerted toxicity at concentrations 3.5% and the maximal toxicity was observed at 5%. The actin cytoskeleton was especially sensitive to glycerol presence, inducing rapid F actin depolymerization at concentrations over 1.5%. The sperm membrane and the mitochondria were other structures affected. The toxicity of glycerol is apparently related to osmotic and nonosmotic effects. In view of our results the concentration of glycerol in the freezing media for stallion spermatozoa should not surpass 2.5%.Funding Agencies|Ministerio de Ciencia e Innovacion-FEDER Madrid, Spain|AGL 2010 20758 (GAN)|Inia|RZ2008-00018-00-00|Junta de Extremadura FEDER GR|10010

A Study of the Prevalence of Asthma in the General Population in Spain

Asma; Epidemiología; PrevalenciaAsthma; Epidemilogy; PrevalenceAsma; Epidemiologia; PrevalençaIntroducción El asma es una enfermedad con elevada prevalencia, que afecta a todos los grupos de edad y genera elevados costes sociosanitarios. Estudios realizados en diversas poblaciones muestran gran variabilidad en su prevalencia, incluso en poblaciones cercanas geográficamente, con datos que sugieren una influencia relevante de factores socioeconómicos. Actualmente en población adulta de España no disponemos de datos poblacionales fiables sobre la prevalencia de esta enfermedad. Los objetivos de este estudio son estimar la prevalencia de asma en población española de 18-79 años, describir la variabilidad entre comunidades autónomas, estimar la prevalencia de infra y sobrediagnóstico, prevalencia de asma no controlada, de asma córticodependiente, conocer el consumo de recursos sanitarios, identificar los fenotipos más frecuentes y establecer un punto de partida para evaluar la tendencia temporal con estudios posteriores. Material y métodos Se realizará un estudio transversal, bietápico, incluyendo pacientes de 50 áreas sanitarias. El estudio se desarrollará en tres fases: 1) cribado y confirmación en historia clínica, en la cual se identificarán los pacientes con diagnóstico previo correctamente establecido de asma; 2) diagnóstico de asma, evaluando a los pacientes en los cuales no está claro el diagnóstico de asma con los datos disponibles en la historia clínica; 3) caracterización del asma, analizando las características de estos pacientes e identificando los fenotipos más frecuentes. Discusión Parece necesario y factible realizar un estudio epidemiológico del asma en España que permita identificar la prevalencia de asma, optimizar la planificación sanitaria, caracterizar los fenotipos más frecuentes de la enfermedad y evaluar los diagnósticos erróneos.Introduction Asthma is a disease with high prevalence, which affects all age groups and generates high health and social care costs. Studies carried out in a number of populations show great variability in its prevalence, even in geographically close populations, with data suggesting a relevant influence of socio-economic factors. At present, we do not have reliable data on the prevalence of this disease in the adult population of Spain. The objectives of this study are to estimate the prevalence of asthma in the Spanish population for those aged 18-79, to describe the variability between autonomous communities, to estimate the prevalence of under and overdiagnosis, to analyse the prevalence of uncontrolled asthma and steroid-dependent asthma, to evaluate the health care cost, to identify the most frequent phenotypes and to establish a starting point to evaluate the temporal trend with subsequent studies. Methods A cross-sectional, two-stage study will be carried out, including patients from 50 catchment areas. The study will be carried out in 3 phases: 1) screening and confirmation in the clinical history, in which patients with a previously correctly established diagnosis of asthma will be identified; 2) diagnosis of asthma to evaluate patients without a confirmed or excluded diagnosis; 3) characterization of asthma, where the characteristics of the asthmatic patients will be analysed, identifying the most frequent phenotypes. Discussion It seems necessary and feasible to carry out an epidemiological study of asthma in Spain to identify the prevalence of asthma, to optimize healthcare planning, to characterize the most frequent phenotypes of the disease, and to evaluate inaccurate diagnoses.Este trabajo ha sido financiado por el Foro Autonómico de Asma-SEPAR