Toxicological assessment of mesoporous silica particles in the nematode Caenorhabditis elegans

[EN] Here we report the toxicological evaluation of mesoporous silica particles (MSPs) in the nematode C. elegans. Specifically, we have investigated the effect of bare micro- (M0) and nano-sized (N0) MSPs, and their corresponding functionalized particles with a starch derivative (Glu-N) (M1 and N1, respectively) on C. elegans ageing parameters. The toxicity of MSPs, their impact on C. elegans lifespan, movement capacity, progeny and ability to survive upon exposure to acute oxidative stress were assessed. This study demonstrated that both size particles assayed (M0 and N0), labeled with rhodamine and monitored through fluorescence microscopy, are ingested by the nematode. Moreover, toxicity assays indicated that bare nano-sized particles (N0) have a negative impact on the C. elegans lifespan, reducing mobility and progeny production. By contrast, micro-sized particles (M0) proved innocuous for the nematodes. Furthermore, functionalization of nanoparticles with starch derivative reduced their toxicity in C. elegans. Thus, oral intake of N1 comparatively increased the mean lifespan and activity rates as well as resistance to oxidative stress. The overall findings presented here demonstrate the influence of MSP size and surface on their potential toxicity in vivo and indicate the silica-based mesoporous particles to be a potential support for encapsulation in oral delivery applications. Furthermore, the good correlation obtained between healthy aging variables and viability (mean lifespan) validates the use of C. elegans as a multicellular organism for nanotoxicology studies of MSPs.The authors wish to express their gratitude to the Spanish Government (MINECO Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02, AGL2015-70235-C2-1, MAT2012-38429-C04-01 and MAT2015-64139-C4-1), the Generalitat Valenciana (Project PROMETEOII/2014/047) and Colombian Administrative Department of Science, Technology and Research which supported Ms. Acosta Scholarship. We would also like to thank the Institut de Ciencia dels Materials (ICMUV), the Microscopy Service of the Universitat Politecnica de Valencia and the microscopy service of IATA for technical support. We thank Roquette for the Glucidex samples.Acosta-Romero, C.; Barat Baviera, JM.; Martínez-Máñez, R.; Sancenón Galarza, F.; Llopis Llopis, S.; Gonzalez, N.; Genovés, S.... (2018). Toxicological assessment of mesoporous silica particles in the nematode Caenorhabditis elegans. Environmental Research. 166:61-70. https://doi.org/10.1016/j.envres.2018.05.018S617016

Adherence to and appropriateness of anti-osteoporotic treatments in patients aged 50 and over in the Valencia Region (Spain). The ESOSVAL-AD Study

<p>Summary</p> <p>Background</p> <p>A study to evaluate the adherence to and appropriateness of anti-osteoporotic treatments in a cohort of men and women aged 50 and over participating in the ESOSVAL-R study.</p> <p>Methods/Design</p> <p><it>Design</it>: An observational, longitudinal, prospective cohort study; Study subjects: Men and women aged 50 and over living in the Valencia Region (Spain) who initiated treatment between June 15, 2009, and June 15, 2011, in primary healthcare centers with electronic medical records; <it>Data sources</it>: The main data source will be electronic medical records. <it>Measurement of results: </it>Degree of compliance with and persistence of anti-osteoporotic treatments, and the proportion of patients with appropriate anti-osteoporotic treatment in accordance with the most relevant and high impact recommendations with clearly defined treatment algorithms in Spain (the Spanish National Health System guide (2010), the General Practitioners' Society (2007) and the General Directorate for Pharmacy and Medical Products of Madrid (2007)), and with the National Osteoporosis Foundation (NOF, 2010), and the International Osteoporosis Foundation guidelines (IOF, 2008); <it>Analysis</it>: 1.) Descriptive analysis of patients undergoing treatment and the treatments prescribed; 2.) Descriptive analysis of compliance with and persistence of anti-osteoporotic treatments; 3.) Analysis of factors associated with compliance with and persistence of treatments by Cox proportional hazard regression models, 4.) Descriptive analysis of appropriateness of treatment; 5.) Analysis of factors associated with the appropriateness of treatment by multilevel models (4 levels: patient, doctor, Basic Healthcare Zone/Primary Healthcare Center, and Health Area variables).</p> <p>Discussion</p> <p>ESOSVAL-AD will provide information regarding adherence to osteoporosis treatments and the factors associated with a higher or lower adherence (including the appropriateness of the treatment) in the Spanish context. A better understanding of this phenomenon and the interventions needed to address it would contribute to the increased effectiveness of therapeutic measures, a reduction in morbidity and mortality, and a corresponding reduction in healthcare costs.</p

Estudio farmacoeconómico del tratamiento antitabáquico en un entorno clínico en Albacete.

Introducción. El coste del tabaquismo en vidas, sufrimiento y dinero es muy importante. El objetivo de nuestro estudio es realizar una evaluación fármaco-económica de los tratamientos utilizados en un entorno clínico en Albacete. Material y métodos. 1484 pacientes que acudieron a la Unidad de Tratamiento Especializado en Tabaquismo del Complejo Hospitalario Universitario de Albacete desde el 1 de Enero de 2008 hasta el 31 de Diciembre de 2012, reali- zándose estudio retrospectivo donde se recogieron variables relacionadas con el éxito y fracaso, además de con el uso de los diferentes tratamientos. Se utilizaron la Chi-cuadrado y la prueba exacta de Fisher. Para variables cuantitativas se utilizó el ANOVA y la V de Cramer para la correlación. Resultados. Los costes por éxito: el psicológico, 583 euros (€); la vareniclina, 1828 €; el bupropion, 1230 € y la TSN, 2038 €. El coste por el paciente que no había fracasado fue de 806 € para la vareniclina, 495 € para el bupropion, 585 € para la TSN y 307 € para la psicológica. Conclusión. Los tratamientos antitabáquicos son medidas eficientes para el sistema sanitario

Dissecting the multifunctional role of the N-terminal disordered domain of a plant virus coat protein in RNA packaging, viral movement and interference with antiviral plant defense

[EN] The coat protein (CP) of Melon necrotic spot virus (MNSV) is structurally composed of three major domains. The middle S-domain builds a robust protein shell around the viral genome, whereas the C-terminal protruding domain, or P-domain, is involved in the attachment of virions to the transmission vector. Here, we have shown that the N-terminal domain, or R-domain, and the arm region, which connects the R-domain and S-domain, are involved in different key steps of the viral cycle, such as cell-to-cell movement and the suppression of RNA silencing and pathogenesis through their RNA-binding capabilities. Deletion mutants revealed that the CP RNA-binding ability was abolished only after complete, but not partial, deletion of the R-domain and the arm region. However, a comparison of the apparent dissociation constants for the CP RNA-binding reaction of several partial deletion mutants showed that the arm region played a more relevant role than the R-domain in in vitro RNA binding. Similar results were obtained in in vivo assays, although, in this case, full-length CPs were required to encapsidate full-length genomes. We also found that the R-domain carboxyl portion and the arm region were essential for efficient cell-to-cell movement, for enhancement of Potato virus X pathogenicity, for suppression of systemic RNA silencing and for binding of small RNAs. Therefore, unlike other carmovirus CPs, the R-domain and the arm region of MNSV CP have acquired, in addition to other essential functions such as genome binding and encapsidation functions, the ability to suppress RNA silencing by preventing systemic small RNA transport.This work was funded by grant BIO2014-54862-R from the Spanish Ministry of Science and Innovation and the Prometeo Program GV2014/010 from the Generalitat Valenciana. J.A.N. and M.S.-S. are the recipients of a postdoctoral contract and a PhD fellowship, respectively, from the Ministerio de Educacion y Ciencia of Spain. We thank L. Corachan for technical assistance. The authors have no conflicts of interest to declare.Serra Soriano, M.; Navarro Bohigues, JA.; Pallás Benet, V. (2017). Dissecting the multifunctional role of the N-terminal disordered domain of a plant virus coat protein in RNA packaging, viral movement and interference with antiviral plant defense. Molecular Plant Pathology. 18(6):837-849. https://doi.org/10.1111/mpp.12448S83784918

Prevalence of vertebral fractures in women and men in the population-based Tromsø Study

<p>Abstract</p> <p>Background</p> <p>Osteoporotic vertebral fractures are, as the hip fractures, associated with increased morbidity and mortality. Norway has one of the highest reported incidences of hip fractures in the world. Because of methodological challenges, vertebral fractures are not extensively studied. The aim of this population based study was to describe, for the first time, the age- and sex specific occurrence of osteoporotic vertebral fractures in Norway.</p> <p>Methods</p> <p>Data was collected in the Tromso Study, 2007/8 survey. By the use of dual x-ray absorptiometry (GE Lunar Prodigy) vertebral fracture assessments were performed in 2887 women and men aged from 38 to 87 years, in addition to measurements of bone mineral density at the femoral sites. Information on lifestyle was collected through questionnaires. Comparisons between fractures and non-fractures were done sex stratified, by univariate analyses, adjusting for age when relevant.</p> <p>Results</p> <p>The prevalence of vertebral fractures varied from about 3% in the age group below 60 to about 19% in the 70+ group in women, and from 7.5% to about 20% in men, with an overall prevalence of 11.8% in women and 13.8% in men (<it>p </it>= 0.07). Among those with fractures, only one fracture was the most common; two and more fractures were present in approximately 30% of the cases. Fractures were seen from the fourth lumbar to the fifth thoracic vertebrae, most common between first lumbar and sixth thoracic vertebrae. The most common type of fracture was the wedge type in both sexes. Bone mineral density at the hip differed significantly according to type of fracture, being highest in those with wedge fractures and lowest in those with compression fractures.</p> <p>Conclusions</p> <p>The prevalence of vertebral fractures increased by age in women and men, but the overall prevalence was lower than expected, considering the high prevalence of hip and forearm fractures in Norway. In both sexes, the wedge type was the fracture type most frequently observed and most common in the thoracic region.</p

Securing the Downside Up: Client and Care Factors Associated with Outcomes of Secure Residential Youth Care

Although secure residential care has the potential of reducing young people's behavioral problems, it is often difficult to achieve positive outcomes. Research suggests that there are several common success factors of treatment, of which the client's motivation for treatment and the quality of the therapeutic relationship between clients and therapists might be especially relevant and important in the context of secure residential care. The objective of the present study was to explore the association of these potential success factors with secure residential care outcomes. A repeated measures research design was applied in the study, including a group of adolescents in a secure residential care center that was followed up on three measurements in time. Interviews and questionnaires concerning care outcomes in terms of adolescents' behavior change during care were administered to 22 adolescents and 27 group care workers. Outcomes in terms of adolescents' treatment satisfaction were assessed by the use of questionnaires, which were completed by 51 adolescents. Adolescents reported some positive changes in their treatment motivation, but those who were more likely to be motivated at admission were also more likely to deteriorate in treatment motivation from admission to departure. Treatment satisfaction was associated with better treatment motivation at admission and with a positive adolescent-group care worker relationship. The results suggest that outcomes can be improved by a more explicit treatment focus on improving the adolescent's treatment motivation and the quality of the adolescent-care worker relationship during secure residential care

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.Part of the research currently in progress in the authors' laboratory is funded by the company Hero Spain, S. A. through the grant #3582 managed by the Fundacion General Empresa-Universidad de Granada

Preventing Violence in Seven Countries: Global Convergence in Policies

Do governments take the measures that are supported by the best scientific evidence available? We present a brief review of the situation in: Australia, Canada, Germany, the Netherlands, Spain, the United Kingdom, and the United States. Our findings show surprisingly similar developments across countries. While all seven countries are moving towards evidence-based decision making regarding policies and programs to prevent violence, there remain a number of difficulties before this end can be achieved. For example, there continue to be few randomized controlled trials or rigorous quasi-experimental studies on aggression and violence. Results from experimental research are essential to both policy makers and researchers to determine the effectiveness of programs as well as increase our knowledge of the problem. Additionally, all noted that media attention for violence is high in their country, often leading to management by crisis with the result that policies are not based on evidence, but instead seek to appease public outrage. And perhaps because of attendant organizational problems (i.e., in many countries violence prevention was not under the guise of one particular agency or ministry), most have not developed a coordinated policy focusing on the prevention of violence and physical aggression. It is hypothesized that leaders in democratic countries, who must run for election every 4 to 6 years, may feel a need to focus on short-term planning rather than long-term preventive policies since the costs, but not the benefits for the latter would be incurred while they still served in office. We also noted a general absence of expertise beyond those within scientific circles. The need for these ideas to be more widely accepted will be an essential ingredient to real and sustaining change. This means that there must be better communication and increased understanding between researchers and policy makers. Toward those ends, the recent establishment of the Campbell Collaboration, formed to provide international systematic reviews of program effectiveness, will make these results more available and accessible to politicians, administrators and those charged with making key policy decision