Interferon induction by avian reovirus

We have previously shown that the replication of avian reovirus (ARV) in chicken embryo fibroblasts (CEF) is more resistant to the antiviral action of interferon (IFN) than the replication of vesicular stomatitis virus (VSV) or vaccinia virus (VV). In this study we examined the capacity of these three viruses to induce the expression of IFN when infecting avian cells. Efficient expression of both type-α and type-β IFNs, as well as of the double-stranded RNA (dsRNA)-activated protein kinase (PKR), takes place in ARV-infected CEF, but not in cells infected with VSV or VV. PKR expression is not directly induced by ARV infection, but by the IFN secreted by ARV-infected cells. IFN induction in ARV-infected cells requires viral uncoating, but not viral gene expression, a situation similar to that reported for apoptosis induction by ARV-infected cells. However, our results demonstrate that IFN induction by ARV-infected CEF occurs by a caspase-independent mechanismThis work was funded by grants from the Spanish Ministerio de Economia y Competitividad (BFU2010-22228 and BFU2013-43513-R) and from the Xunta de Galicia (CN 2012/018). I.L.S. was a recipient of a predoctoral FPU fellowship (Ministerio de Educación y Ciencia) and a Research Fellowship (Bolsa de Investigación) (Deputación Provincial da Coruña)S

Response of Three Different Viruses to Interferon Priming and Dithiothreitol Treatment of Avian Cells

We have previously shown that the replication of avian reovirus (ARV) in chicken cells is much more resistant to interferon (IFN) than the replication of vesicular stomatitis virus (VSV) or vaccinia virus (VV). In this study, we have investigated the role that the double-stranded RNA (dsRNA)-activated protein kinase (PKR) plays in the sensitivity of these three viruses toward the antiviral action of chicken interferon. Our data suggest that while interferon priming of avian cells blocks vaccinia virus replication by promoting PKR activation, the replication of vesicular stomatitis virus appears to be blocked at a pretranslational step. Our data further suggest that the replication of avian reovirus in chicken cells is quite resistant to interferon priming because this virus uses strategies to downregulate PKR activation and also because translation of avian reovirus mRNAs is more resistant to phosphorylation of the alpha subunit of initiation factor eIF2 than translation of their cellular counterparts. Our results further reveal that the avian reovirus protein sigmaA is able to prevent PKR activation and that this function is dependent on its double-stranded RNA-binding activity. Finally, this study demonstrates that vaccinia virus and avian reovirus, but not vesicular stomatitis virus, express/induce factors that counteract the ability of dithiothreitol to promote eIF2 phosphorylation. Our data demonstrate that each of the three different viruses used in this study elicits distinct responses to interferon and to dithiothreitol-induced eIF2 phosphorylation when infecting avian cellsThe Spanish Ministerio de Economía y Competitividad provided funding to Javier Benavente and José Martínez-Costas under grant numbers BFU2010-22228 and BFU2013-43513-R. Support was also provided by the Xunta de Galicia (CN 2012/018). Irene Lostalé-Seijo was a recipient of a predoctoral FPU fellowship (Ministerio de Educación y Ciencia) and a Research Fellowship (Bolsa de Investigación; Deputación Provincial da Coruña)S

Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin

A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasm sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cellsThis research was supported by grants from the Spanish Ministerio de Ciencia y Tecnología (BFU2007-61330/BMC) and from the Xunta de Galicia (08CSA009203PR). L. V-I. and I. L-S. were recipients of predoctoral fellowships from the FPI and FPU programs of the Spanish Ministerio de Ciencia y TecnologíaS

Self-paced cycling improves cognition on institutionalized older adults without known cognitive impairment: A 15-month randomized controlled trial

This study aimed at identifying the effects of self-paced cycling on the cognitive and functional status and fall risk on institutionalized older adults without cognitive impairment. A total of 39 individuals were randomly assigned to an exercise group or to a control group. The exercise group participants cycled at their self-selected intensity at least for 15 min daily during 15 months. The control group participants performed recreational activities. The Mini-Mental State Examination, Fuld object memory evaluation, and symbol digit modality test were used for cognitive assessments. The Katz index, the timed "Up & Go" test, and the World Health Organization questionnaire were used to assess functional independence, mobility, and fall risk. Significant improvements were observed in the exercise group for global cognition and attention, visual scanning, and processing speed. Long-term self-paced cycling training seems to have a protective effect on cognitive status and attention, visual scanning, and processing speed in older institutionalized individuals

IC-Tagging methodology applied to the expression of viral glycoproteins and the difficult-to-express membrane-bound IGRP autoantigen

We have previously developed a methodology to produce protein microspheres (MS) that can be loaded with proteins of interest in living cells through their C or N-terminal tagging with the so-called IC-Tag. The IC-Tagging method has many applications ranging from the production of immobilized enzymes for industrial use to the production of subunit vaccines due to its intrinsic adjuvancy. Here we show the adaptation of the IC-Tagging to work inside the endoplasmic reticulum and bacteria, allowing us to produce properly modified viral glycoproteins. Additionally, we were able to express the Islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP), whose expression remained elusive to date possibly due to its toxicity when over-expressed. IGRP is an antigen of enormous pharmaceutical interest as it is specifically targeted during the autoimmune response taking place in both the Non-Obese Diabetic (NOD) mice and type 1 diabetes (T1D) patients leading to the destruction of insulin-producing beta cellsThis work was financed by the Spanish Ministerio de Economía y Competitividad, grant BFU2013-43513-R. Financial support from the Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2016–2019) and the European Union (European Regional Development Fund - ERDF), is gratefully acknowledged. Irene Lostalé-Seijo was a recipient of a predoctoral FPU fellowship (Ministerio de Educación y Ciencia) and a Research Fellowship (Bolsa de Investigación; Deputación Provincial da Coruña)S

Consequences of child maltreatment victimisation in internalising and externalising mental health problems

Purpose: The literature on the prevalence of child maltreatment is extensive, but studies are required to assess the impact on mental health to enhance the effectiveness of intervention programs. Method: Thus, a field study was undertaken to evaluate depression, anxiety, and anger in 65 child victims of multiple types of maltreatment. Results: The results showed that child maltreatment victim (CM-V) reported more depressive (36%), anxiety (45%), and anger (69%) symptoms than the normative sample. However, subjects were asymptomatic in approximately 25% of depression, 20% anxiety, and 5% of anger. Epidemiologically, the results revealed that the probability of caseness among the CM-Vs sample increased to around 85% for depression and anxiety and 90% for anger.Conclusions: The clinical, social, and legal implications of the results are discussedThis research has been partially sponsored by a grant of the Consellería de Cultura, Educación e Ordenación Universitaria of the Xunta de Galicia (ED431B 2020/46), and by a grant of the Spanish Ministry of Science and Innovation (PSI2017-87278-R)S

Profiling small scale domestic grower cannabis users

El cannabis es la sustancia ilícita más consumida a nivel mun-dial, con una prevalencia estimada entre el 2.8 y el 5.0% de la población adulta. El auge del consumo de cannabis ha llevado a un aumento en el cul-tivo para el propio consumo. Como consecuencia, nos planteamos un es-tudio de campo con el objetivo de contrastar si consumidores con y sin au-tocultivo se diferencian en el perfil sociodemográfico, patrones de consu-mo, riesgo de consumo problemático, dependencia, y síntomas y trastornos asociados. Para ello, 761 consumidores de cannabis, 480 hombres y 281 mujeres, de los cuales 251 autocultivaban para su consumo (182 hombres y 69 mujeres), con edades comprendidas entre los 18 y 60 años (M = 26.36, DT = 5.68), respondieron a un cuestionario sociodemográfico y de patro-nes de consumo, a escalas de medida del consumo problemático de canna-bis, dependencia del cannabis, abuso del cannabis, y de dependencia de la nicotina y del alcohol. Los resultados mostraron que el autocultivo es ca-racterístico mayoritariamente de los varones, con bajo nivel académico y laboralmente activos. Asimismo, la práctica del autocultivo se relaciona con un mayor consumo de cannabis, una mayor implicación en la venta ilegal del producto, policonsumo y con problemáticas psicosociales derivadas de dicho consumo. Adicionalmente, los que autocultivan informan de mayo-res niveles de dependencia y de riesgo de consumo problemático de canna-bis. Se discuten las implicaciones para la prevención y tratamiento de los trastornos por consumo de cannabisCannabis is the most widely used worldwide drug with preva-lence between 2.8 and 5.0% of the adult population. Increasing use of can-nabis has carried out to an escalation in home growing for self-consumption. As a consequence, a field study to contrast if the domestic cannabis growers exhibited a different sociodemographic profile, a con-sumption pattern, a problematic use risk, dependence level, as well as on the clinical symptoms and related disorders, was designed. As for this, 761 cannabis users, 480 males and 281 females, of whom 251 were homegrow-ers for personal use (182 males and 69 females), with ages ranging from 18 to 60 years (M = 26.36, SD = 5.68), answered to a sociodemohgraphic and consumption pattern questionnaire, and to cannabis problematic use, can-nabis dependence, cannabis abuse, and nicotine and alcohol dependence scales. The results showed that homegrowers are mostly males, with low academic training and working. Moreover, homegrowers have a higher cannabis consumption rates, are more implied in cannabis selling, polysub-stance use, and with more psychosocial problem driven from cannabis use. Finally, homegrowers inform of higher problematic cannabis use and a higher level of cannabis dependence. The implications of the results for prevention police, and treatment of the cannabis use disorder are dis-cussedS

A protective personal factor against disability and dependence in the elderly: an ordinal regression analysis with nine geographically-defined samples from Spain

Background: Sense of Coherence (SOC) is defined as a tendency to perceive life experiences as comprehensible, manageable and meaningful. The construct is split in three major domains: Comprehensibility, Manageability, and Meaningfulness. SOC has been associated with successful coping strategies in the face of illness and traumatic events and is a predictor of self-reported and objective health in a variety of contexts. In the present study we aim to evaluate the association of SOC with disability and dependence in Spanish elders. Methods: A total of 377 participants aged 75 years or over from nine locations across Spain participated in the study (Mean age: 80.9 years; 65.3% women). SOC levels were considered independent variables in two ordinal logistic models on disability and dependence, respectively. Disability was established with the World health Organization-Disability Assessment Schedule 2.0 (36-item version), while dependence was measured with the Extended Katz Index on personal and instrumental activities of daily living. The models included personal (sex, age, social contacts, availability of an intimate confidant), environmental (municipality size, access to social resources) and health-related covariates (morbidity). Results: High Meaningfulness was a strong protective factor against both disability (Odds Ratio [OR] = 0.50; 95% Confidence Interval [CI] = 0.29-0.87) and dependence (OR = 0.33; 95% CI = 0.19-0.58) while moderate and high Comprehensibility was protective for disability (OR = 0.40; 95% CI = 0.22-0.70 and OR = 0.39; 95% CI = 0.21-0.74), but not for dependence. Easy access to social and health resources was also highly protective against both disability and dependence. Conclusions: Our results are consistent with the view that high levels of SOC are protective against disability and dependence in the elderly. Elderly individuals with limited access to social and health resources and with low SOC may be a group at risk for dependence and disability in Spain

Prevalence of dementia and major dementia subtypes in Spanish populations: A reanalysis of dementia prevalence surveys, 1990-2008

Background This study describes the prevalence of dementia and major dementia subtypes in Spanish elderly. Methods We identified screening surveys, both published and unpublished, in Spanish populations, which fulfilled specific quality criteria and targeted prevalence of dementia in populations aged 70 years and above. Surveys covering 13 geographically different populations were selected (prevalence period: 1990-2008). Authors of original surveys provided methodological details of their studies through a systematic questionnaire and also raw age-specific data. Prevalence data were compared using direct adjustment and logistic regression. Results The reanalyzed study population (aged 70 year and above) was composed of Central and North-Eastern Spanish sub-populations obtained from 9 surveys and totaled 12,232 persons and 1,194 cases of dementia (707 of Alzheimer's disease, 238 of vascular dementia). Results showed high variation in age- and sex-specific prevalence across studies. The reanalyzed prevalence of dementia was significantly higher in women; increased with age, particularly for Alzheimer's disease; and displayed a significant geographical variation among men. Prevalence was lowest in surveys reporting participation below 85%, studies referred to urban-mixed populations and populations diagnosed by psychiatrists. Conclusion Prevalence of dementia and Alzheimer's disease in Central and North-Eastern Spain is higher in females, increases with age, and displays considerable geographic variation that may be method-related. People suffering from dementia and Alzheimer's disease in Spain may approach 600,000 and 400,000 respectively. However, existing studies may not be completely appropriate to infer prevalence of dementia and its subtypes in Spain until surveys in Southern Spain are conductedFinancial aid was obtained from the Spanish RECSP C03-09, CIEN C03-06 and CIBERNED networks, and from the Pfizer Foundation in particularS

Falls predict acute hospitalization in Parkinson's disease

Background: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission. Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort. Methods: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit. Results: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065-5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319-6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757-8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124-4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080-8.322; p = 0.035) was an independent predictor of AH. Conclusion: Falls is an independent predictor of AH in PD patients