A Cytoplasmic RNA Virus Alters the Function of the Cell Splicing Protein SRSF2

ABSTRACT To replicate efficiently, viruses must create favorable cell conditions and overcome cell antiviral responses. We previously reported that the reovirus protein μ2 from strain T1L, but not strain T3D, represses one antiviral response: alpha/beta interferon signaling. We report here that T1L, but not T3D, μ2 localizes to nuclear speckles, where it forms a complex with the mRNA splicing factor SRSF2 and alters its subnuclear localization. Reovirus replicates in cytoplasmic viral factories, and there is no evidence that reovirus genomic or messenger RNAs are spliced, suggesting that T1L μ2 might target splicing of cell RNAs. Indeed, RNA sequencing revealed that reovirus T1L, but not T3D, infection alters the splicing of transcripts for host genes involved in mRNA posttranscriptional modifications. Moreover, depletion of SRSF2 enhanced reovirus replication and cytopathic effect, suggesting that T1L μ2 modulation of splicing benefits the virus. This provides the first report of viral antagonism of the splicing factor SRSF2 and identifies the viral protein that determines strain-specific differences in cell RNA splicing. IMPORTANCE Efficient viral replication requires that the virus create favorable cell conditions. Many viruses accomplish this by repressing specific antiviral responses. We demonstrate here that some mammalian reoviruses, RNA viruses that replicate strictly in the cytoplasm, express a protein variant that localizes to nuclear speckles, where it targets a cell mRNA splicing factor. Infection with a reovirus strain that targets this splicing factor alters splicing of cell mRNAs involved in the maturation of many other cell mRNAs. Depletion of this cell splicing factor enhances reovirus replication and cytopathic effect. Our results provide the first evidence of viral antagonism of this splicing factor and suggest that downstream consequences to the cell are global and benefit the virus

Origin and Control Strategies of Biofilms in the Cultural Heritage

Biodeterioration is defined as the undesirable change in the properties of materials caused by the activity of biological agents. This process is complex and involves alterations in the physicochemical and mechanical properties by the action of organisms and depends on the microorganisms involved, type of substrate, and environmental conditions. The biodeterioration of cultural heritage is the physical or chemical damage caused by microorganisms on objects, monuments, or buildings that belong to the cultural heritage. Among the main materials that can be affected are: stone, metal, ceramic, polymers, and other materials. Among the main undesirable effects to these materials are: discoloration, dissolution, rupture, and efflorescence among others. Biofilms represent the usual form of growth of bacteria and consist of communities of microorganisms that grow attached to an inert surface or a living tissue, surrounded by an extracellular matrix that they themselves synthesize. The importance of biodeterioration by biofilms is mainly related to changes in pH values, ionic concentrations, oxide-reduction reactions in the biofilm thickness, and in the interface with the substrate and enzymatic degradation. This chapter presents evidence of the participation of biofilms and associated mechanisms in biodeterioration as well as the main prevention and control strategies

Protein composition of the hepatitis A virus quasi-envelope

The nonlytic cellular egress of picornaviruses in extracellular vesicles is likely to be important in disease pathogenesis, but the mechanism(s) underlying this process and the origins of the membranes surrounding virions exiting the cell are poorly understood. We describe a quantitative proteomics analysis of quasi-enveloped hepatitis A virus (eHAV) virions that shows capsids are selected as cargo for vesicular export via a highly specific process, and that infectious eHAV virions possess a host protein complement similar to that of exosomes with CD9 and DPP4 displayed on their surface. eHAV-associated proteins are highly enriched for endolysosomal components and lack markers of autophagy, suggesting an exosome-like mechanism of endosomal sorting complex required for transport-mediated eHAV biogenesis involving endosomal budding that is distinct from the autophagosome-mediated release proposed previously for enteroviruses

An educational initiative for Mexican school-aged children to promote the consumption of fruit, vegetables and physical activity

Aim: To present the results of a community initiative focused on strengthening physical activity and the consumption of fruits, vegetables and natural water while discouraging the use of highly energetic food and sugary drinks in public schools of Morelos. Methods: A quasi-experimental study with an educational initiative focused on the school community of two primary schools and two junior high schools. Pre- and-post initiative measurements were made. The study took place in the municipality of Yautepec, Morelos, Mexico, in a rural area and an urban area, from August 2010 to July 2011.   Results: Water consumption among school-aged children increased from 15.1% to 20.1% and soda consumption decreased from 21.4% to 13.2%. A slight increase in the consumption of fruits and vegetables was also measured (oranges, jicamas, bananas, tomatoes, prickly pear pads, lettuces), that are accessible in the region. It was found that the supply of fresh food is limited and that high energy density foods have an oversupply in both study areas. Physical activity increased with actions such as football and dancing, in accordance with the baseline measurement. No changes were observed in the nutritional condition of school-aged children (n=150; 13.3% with overweight and 7.3% with emaciation), or in adults who presented a body mass index higher than normal, 60.2% to 88.4%. Conclusion: In addition to educational activities, schools need to implement strategies to improve the access and availability of fresh foods while limiting the access of high energy-density foods.   &nbsp

Evaluation of the efficacy and safety of text messages targeting adherence to cardiovascular medications in secondary prevention: the txt2heart Colombia randomised controlled trial (Preprint)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in the world. Prevalence is estimated at around 100 million patients worldwide. There is evidence that antiplatelet agents and antihypertensive medication reduce the risk of new vascular events in this population, but treatment adherence is very low. Objective: We developed an intervention based on behavioral modification techniques delivered via mobile short message services (SMS) to increase the adherence to pharmacologic treatment on patients with prior history of ASCVD. Methods: We conducted a randomized controlled clinical trial for patients with a prior diagnosis of cardiovascular event such as acute myocardial infarction, unstable angina, cerebrovascular disease or peripheral artery disease in one centre in Colombia. Patients randomized to the intervention arm were assigned to receive SMS daily for the first 4 weeks, five SMS on week 5: three SMS per week from week 6, and one SMS from 8th week until 52nd week. Patients in the control arm received a monthly SMS reminding them of the next study appointment, requesting information about changes in phone number, thanking them for participating in the study and reminding them of the importance of the study. Primary endpoint was change in Low Density Lipoprotein-Cholesterol (LDL-C) and the secondary endpoints were change in thromboxane B2 levels, heart rate, systolic and diastolic blood pressure. Medication adherence was measured with the Medication Adherence Report Scale (MARS 5), mortality and new cardiac hospitalization were assessed at one year end point. A logistic regression analysis and bivariate testing was performed. Results: Nine hundred and thirty patients were randomized, 805 (87%) completed follow up, and were analyzed for the primary endpoint. There was no difference between arms in change of LDL-C at 12 months (P=.41). or for any of the secondary outcomes. No adverse events were reported. Conclusions: In our study we did not find evidence that a behavior modification intervention delivered by SMS improved LDL-C, blood pressure levels or adherence at 12 months. More research is needed to evaluate whether different SMS strategies including personalized messages and with different timing are effective; future studies should include mixed methods to understand better why, for whom and in which context (e.g. health system, social environment) SMS interventions work (or not) to improve adherence in patients with ASCVD. Clinical Trial: Clinicaltrial.gov NCT03098186. Date of registration: March 31st 201

An educational initiative for Mexican school-aged children to promote the consumption of fruit, vegetables and physical activity

Aim: To present the results of a community initiative focused on strengthening physical activity and the consumption of fruits, vegetables and natural water while discouraging the use of highly energetic food and sugary drinks in public schools of Morelos.Methods: A quasi-experimental study with an educational initiative focused on the school community of two primary schools and two junior high schools. Pre- and-post initiative measurements were made. The study took place in the municipality of Yautepec, Morelos, Mexico, in a rural area and an urban area, from August 2010 to July 2011.  Results: Water consumption among school-aged children increased from 15.1% to 20.1% and soda consumption decreased from 21.4% to 13.2%. A slight increase in the consumption of fruits and vegetables was also measured (oranges, jicamas, bananas, tomatoes, prickly pear pads, lettuces), that are accessible in the region. It was found that the supply of fresh food is limited and that high energy density foods have an oversupply in both study areas. Physical activity increased with actions such as football and dancing, in accordance with the baseline measurement. No changes were observed in the nutritional condition of school-aged children (n=150; 13.3% with overweight and 7.3% with emaciation), or in adults who presented a body mass index higher than normal, 60.2% to 88.4%.Conclusion: In addition to educational activities, schools need to implement strategies to improve the access and availability of fresh foods while limiting the access of high energy-density foods.  

Effectiveness of a psycho-educational program for improving quality of life of fibromyalgia patients

<p>Abstract</p> <p>Background</p> <p>Most fibromyalgia patients are seen in primary care (PC). However, the effectiveness of the treatments prescribed by general practitioners is usually minimal. The main objective of the present research is to assess the efficacy of structured psycho-educational intervention, combined with relaxation, developed to improve the quality of life of patients suffering fibromyalgia (FM). The second objective is to assess the cost-effectiveness of this multimodal intervention.</p> <p>Method/Design</p> <p><it>Design</it>. Randomized controlled trial with a 12-month follow-up involving two groups, one of which is the intervention group that includes patients receiving a psychoeducational program and the other the control group consisting of patients treated for FM in the usual way.</p> <p><it>Setting</it>. Three urban PC centers in the province of Barcelona (Spain).</p> <p><it>Sample</it>. The total sample comprises 218 patients (over 18 years of age) suffering FM, selected from a database (Rheumatology service-Viladecans Hospital) of patients with this illness. Only those patients introduced in the database between the years 2005 and 2007 were included in the selection. Selected patients will be asked for written informed consent to participate in the study.</p> <p><it>Intervention</it>. Multi-component program including information about the illness, counselling about physical exercise and training in autogenic relaxation. The intervention consists of nine 2-hour sessions delivered during a two-month period. The pharmacological treatment prescribed by the physician was maintained in both groups.</p> <p><it>Main variables</it>. Sociodemographic characteristics, quality of life, use and cost of healthcare and social services.</p> <p><it>Measures</it>. Quality of life is to be measured with the FIQ and the EuroQol-5D, and the use of healthcare services with an adapted version of the Client Service Receipt Inventory (CSRI). These variables will be measured before the beginning of the program (baseline) and 1, 2, 6 and 12 months later.</p> <p>Discussion</p> <p>This research project is an attempt to demonstrate that a psycho-educational program implemented in the context of PC can produce a significant increase in the quality of life for patients with FM, as well as a decrease in the use of healthcare and social services, compared with usual care.</p> <p>Trial registration</p> <p>NCT00550966</p

Resultados clínicos en receptores de trasplante renal posterior a la conversión a ImTOR

Introducción: los ImTOR, sirolimus y everolimus son una alternativa de inmunosupresión en personas que han recibido transplantes rena-les. En este artículo, se describe la experiencia de pacientes que han experimentado una conversión a ImTOR, y a los que se les ha hecho un seguimiento por más de cinco años.Materiales y métodos: se incluyeron pacientes con transplantes renales desde 1995 hasta 2013, quienes tuvieron indicación de suspensión del inhibidor de calcineurina (ICN) después del tercer mes posterior al trasplante. Todos los pacientes fueron sometidos a biopsia renal antes de la administración de ImTOR. Ningún paciente tuvo diagnóstico de nefropatía crónica, IFTA >40 % o proteinuria >350 mg/24h. Se elaboró un análisis descriptivo para todas las variables. Para estudiar la supervivencia del paciente y del injerto, y la incidencia de rechazo agudo, se usó el método de Kaplan-Meier.Resultados: de 1273 trasplantes renales, la conversión de ICN a ImTOR se realizó en 166 casos (13 %). Al 78 % (n=129) se le administró sirolimus. El 13 % de los pacientes perdió la función del injerto y 7 pacientes (4,2 %) fallecieron. En el 37 % de los casos, se retiró el ImTOR. La principal causa de retiro fue el hallazgo de proteinuria patológica. La incidencia de rechazo agudo después del cambio a ImTOR fue de 9,6 %. La supervivencia del injerto tras uno y cinco años fue de 96,6 % y 83,5 %, respectivamente; y la supervivencia del paciente a uno y cinco años fue de 98 % y 97 %, respectivamente.Conclusiones: el uso de inhibidores ImTOR parece ser seguro en este grupo de pacientes trasplantados, pues hubo una baja tasa de rechazo y buena supervivencia del injert

Characterising droughts in Central America with uncertain hydro-meteorological data

Central America is frequently affected by droughts that cause significant socio-economic and environmental problems. Drought characterisation, monitoring and forecasting are potentially useful to support water resource management. Drought indices are designed for these purposes, but their ability to characterise droughts depends on the characteristics of the regional climate and the quality of the available data. Local comprehensive and high-quality observational networks of meteorological and hydrological data are not available, which limits the choice of drought indices and makes it important to assess available datasets. This study evaluated which combinations of drought index and meteorological dataset were most suitable for characterising droughts in the region. We evaluated the standardised precipitation index (SPI), a modified version of the deciles index (DI), the standardised precipitation evapotranspiration index (SPEI) and the effective drought index (EDI). These were calculated using precipitation data from the Climate Hazards Group Infra-Red Precipitation with Station (CHIRPS), the CRN073 dataset, the Climate Research Unit (CRU), ECMWF Reanalysis (ERA-Interim) and a regional station dataset, and temperature from the CRU and ERA-Interim datasets. The gridded meteorological precipitation datasets were compared to assess how well they captured key features of the regional climate. The performance of all the drought indices calculated with all the meteorological datasets was then evaluated against a drought index calculated using river discharge data. Results showed that the selection of database was more important than the selection of drought index and that the best combinations were the EDI and DI calculated with CHIRPS and CRN073. Results also highlighted the importance of including indices like SPEI for drought assessment in Central America.Universidad de Costa Rica/[805-B0-810]/UCR/Costa RicaUniversidad de Costa Rica/[805-A9-532]/UCR/Costa RicaUniversidad de Costa Rica/[805-B3-600]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-065]/UCR/Costa RicaUniversidad de Costa Rica/[805-B3-413]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-227]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-228]/UCR/Costa RicaUniversidad de Costa Rica/[805-B5-295]/UCR/Costa RicaUppsala University/[54100006]//SueciaMarie Curie Intra-European Fellowship/[No.329762]//EuropaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Físic

Cut-offs and response criteria for the Hospital Universitario la Princesa Index (HUPI) and their comparison to widely-used indices of disease activity in rheumatoid arthritis

Objective To estimate cut-off points and to establish response criteria for the Hospital Universitario La Princesa Index (HUPI) in patients with chronic polyarthritis. Methods Two cohorts, one of early arthritis (Princesa Early Arthritis Register Longitudinal PEARL] study) and other of long-term rheumatoid arthritis (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide EMECAR]) including altogether 1200 patients were used to determine cut-off values for remission, and for low, moderate and high activity through receiver operating curve (ROC) analysis. The areas under ROC (AUC) were compared to those of validated indexes (SDAI, CDAI, DAS28). ROC analysis was also applied to establish minimal and relevant clinical improvement for HUPI. Results The best cut-off points for HUPI are 2, 5 and 9, classifying RA activity as remission if =2, low disease activity if >2 and =5), moderate if >5 and <9 and high if =9. HUPI''s AUC to discriminate between low-moderate activity was 0.909 and between moderate-high activity 0.887. DAS28''s AUCs were 0.887 and 0.846, respectively; both indices had higher accuracy than SDAI (AUCs: 0.832 and 0.756) and CDAI (AUCs: 0.789 and 0.728). HUPI discriminates remission better than DAS28-ESR in early arthritis, but similarly to SDAI. The HUPI cut-off for minimal clinical improvement was established at 2 and for relevant clinical improvement at 4. Response criteria were established based on these cut-off values. Conclusions The cut-offs proposed for HUPI perform adequately in patients with either early or long term arthritis