96 research outputs found
La Familia Telerín: Connected Learning through Transmedia
Nowadays, transmedia storytelling has shaped new ways to produce children’s content, in which the audience has an increasingly active role (Livingstone and Bovill 2013; Cortesi et al. 2015). The fruition of storytelling content through digital media allows to connect it with personal interests and school activitiesas well as to enhance the link between adults and children (Ito et al. 2013; Jenkins, Īto, and boyd 2015). The main goal of this paper is to analyze the new transmedia release of one the most successful and recognized TV cartoons all over Spain and Latin America: La Familia Telerín. Specifically, we want to discover how the cartoon was re-valued by the production company Anima Kitchen, and understand the role that transmedia storytelling played out in this regard. Adopting a digital anthropology approach (Horst and Miller 2012), our findings come from big data, a focus group and through a virtual ethnography. The findings provide us with a clear understanding about how transmedia storytelling supports social values, media skills and learning activities into the everyday life of children
Coordination of mitochondrial and lysosomal homeostasis mitigates inflammation and muscle atrophy during aging
Sarcopenia is one of the main factors contributing to disability of aged people. Among the possible molecular determinants of sarcopenia, increasing evidences suggest that chronic inflammation contributes to its development. However, a key unresolved question is the nature of the factors that drive inflammation during aging and that participate in the development of sarcopenia. In this regard, mitochondrial dysfunction and alterations in mitophagy induce inflammatory responses in a wide range of cells and tissues. However, whether accumulation of damaged mitochondria in muscle could trigger inflammation in the context of aging is still unknown. Here, we demonstrate that BNIP3 plays a key role in the control of mitochondrial and lysosomal homeostasis, and mitigates muscle inflammation and atrophy during aging. We show that muscle BNIP3 expression increases during aging in mice and in some humans. BNIP3 deficiency alters mitochondrial function, decreases mitophagic flux and, surprisingly, induces lysosomal dysfunction, leading to an upregulation of TLR9-dependent inflammation and activation of the NLRP3 inflammasome in muscle cells and mouse muscle. Importantly, downregulation of muscle BNIP3 in aged mice exacerbates inflammation and muscle atrophy, and high BNIP3 expression in aged human subjects associates with a low inflammatory profile, suggesting a protective role for BNIP3 against age-induced muscle inflammation in mouse and humans. Taken together, our data allows us to propose a new adaptive mechanism involving the mitophagy protein BNIP3, which links mitochondrial and lysosomal homeostasis with inflammation and is key in maintaining muscle health during aging
Functional Traits in Lichen Ecology: A Review of Challenge and Opportunity
Community ecology has experienced a major transition, from a focus on patterns in taxonomic composition, to revealing the processes underlying community assembly through the analysis of species functional traits. The power of the functional trait approach is its generality, predictive capacity such as with respect to environmental change, and, through linkage of response and effect traits, the synthesis of community assembly with ecosystem function and services. Lichens are a potentially rich source of information about how traits govern community structure and function, thereby creating opportunity to better integrate lichens into ‘mainstream’ ecological studies, while lichen ecology and conservation can also benefit from using the trait approach as an investigative tool. This paper brings together a range of author perspectives to review the use of traits in lichenology, particularly with respect to European ecosystems from the Mediterranean to the Arctic-Alpine. It emphasizes the types of traits that lichenologists have used in their studies, both response and effect, the bundling of traits towards the evolution of life-history strategies, and the critical importance of scale (both spatial and temporal) in functional trait ecology.info:eu-repo/semantics/publishedVersio
Implications of global pricing policies on access to innovative drugs: : the case of trastuzumab in seven Latin American countries
Background: Differential pricing, based on countries’ purchasing power, is recommended by the WHO to secure affordable medicines. However, in developing countries innovative drugs often have similar or even higher prices than in high-income countries. We evaluated the potential implications of trastuzumab global pricing policies in terms of cost-effectiveness (CE), coverage and accessibility for patients with breast cancer in Latin America (LA). Methods: A Markov model was designed to estimate life years (LYs), quality-adjusted life years (QALYs) and costs from a health care perspective. To better fit local cancer prognosis, a base case scenario using transition probabilities from clinical trials was complemented with two alternative scenarios with transition probabilities adjusted to reflect breast cancer epidemiology in each country. Findings: Incremental discounted benefits ranged from 0.87 to 1.00 LY and 0.51 to 0.60 QALY and incremental CE ratios from USD 42,104 to USD 110,283 per QALY (2012 US dollars), equivalent to 3.6 gross domestic product per capita (GDPPC) per QALY in Uruguay and to 35.5 GDPPC in Bolivia. Probabilistic sensitivity analysis showed 0% probability that trastuzumab is CE if the willingness-to-pay (WTP) threshold is one GDPPC per QALY, and remained so at three GDPPC threshold except for Chile and Uruguay (4.3% and 26.6% respectively). Trastuzumab price would need to decrease between 69.6% to 94.9% to became CE in LA. Interpretation: Although CE in other settings, trastuzumab was not CE in LA. The use of health technology assessment to prioritize resource allocation and support price negotiations is critical to making innovative drugs available and affordable in developing countries
Enhanced In Vivo Activity of Cefditoren in Pre-Immunized Mice against Penicillin-Resistant S. pneumoniae (Serotypes 6B, 19F and 23F) in a Sepsis Model
Background
Specific antibodies are likely to be present before S. pneumoniae infection. We explored cefditoren (CDN) total and free values of serum concentrations exceeding the MIC (t>MIC) related to efficacy in a mice sepsis model, and the effect of specific gammaglobulins on in-vitro phagocytosis and in-vivo efficacy.
Methodology/Principal Findings
We used three pneumococcal isolates (serotype, MIC of CDN): Strain 1 (6B, 1 µg/ml), Strain 2 (19F, 2 µg/ml) and Strain 3 (23F, 4 µg/ml). Hyperimmune serum (HS) was obtained from mice immunized with heat-inactivated strains. In-vitro, phagocytosis by HS diluted 1/10 in presence/absence of sub-inhibitory concentrations was measured by flow cytometry including fluorescent bacteria and a neutrophil cell line. In-vivo dose-ranging experiments with HS (dilutions 1/2–1/16) and CDN (6.25 mg/kg–100 mg/kg tid for 48 h) were performed to determine the minimal protective dilution/dose (highest survival) and the non-protective highest dilution/dose (highest mortality: HS-np dilution and CDN-np dose) over 7 days. Efficacy of CDN-np in animals pre-immunized with HS-np (combined strategy) was explored and blood bacterial clearance determined. The CDN measured protein binding was 86.9%. In-vitro, CDN significantly increased phagocytosis (vs. HS 1/10). In non pre-immunized animals, t>MIC values for CDN of ≈35% (total) and ≈19% (free) were associated with 100% survival. Significant differences in survival were found between HS-np alone (≤20%) or CDN-np alone (≤20%) vs. the combined strategy (90%, 60% and 60% for Stains 1, 2 and 3), with t>MIC (total/free) of 22.8%/14.3%, 26.8%/16.0%, and 22.4%/12.7% for Strains 1, 2 and 3, respectively. Prior to the second dose (8 h), median bacterial counts were significantly lower in animals surviving vs. dead at day 7.
Conclusions/Significance
In mice (CDN protein binding similar to humans) total t>MIC values of ≈35% (≈19% free) were efficacious, with a decrease in the required values in pre-immunized animals. This reinforces that immunoprotection to overcome resistance may provide lifesaving strategies.This study was supported by an unrestricted grant from Tedec-Meiji Farma S.A., Madrid, Spain. Tedec-Meiji Farma S.A. had a role in providing reagents, materials and analysis toolsPeer reviewe
Obstetric outcomes of sars-cov-2 infection in asymptomatic pregnant women
Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER)Around two percent of asymptomatic women in labor test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Spain. Families and care providers face childbirth with uncertainty. We determined if SARS-CoV-2 infection at delivery among asymptomatic mothers had different obstetric outcomes compared to negative patients. This was a multicenter prospective study based on universal antenatal screening for SARS-CoV-2 infection. A total of 42 hospitals tested women admitted for delivery using polymerase chain reaction, from March to May 2020. We included positive mothers and a sample of negative mothers asymptomatic throughout the antenatal period, with 6-week postpartum follow-up. Association between SARS-CoV-2 and obstetric outcomes was evaluated by multivariate logistic regression analyses. In total, 174 asymptomatic SARS-CoV-2 positive pregnancies were compared with 430 asymptomatic negative pregnancies. No differences were observed between both groups in key maternal and neonatal outcomes at delivery and follow-up, with the exception of prelabor rupture of membranes at term (adjusted odds ratio 1.88, 95% confidence interval 1.13-3.11; p = 0.015). Asymptomatic SARS-CoV-2 positive mothers have higher odds of prelabor rupture of membranes at term, without an increase in perinatal complications, compared to negative mothers. Pregnant women testing positive for SARS-CoV-2 at admission for delivery should be reassured by their healthcare workers in the absence of symptoms
Association of Candidate Gene Polymorphisms With Chronic Kidney Disease: Results of a Case-Control Analysis in the Nefrona Cohort
Chronic kidney disease (CKD) is a major risk factor for end-stage renal disease, cardiovascular disease and premature death. Despite classical clinical risk factors for CKD and some genetic risk factors have been identified, the residual risk observed in prediction models is still high. Therefore, new risk factors need to be identified in order to better predict the risk of CKD in the population. Here, we analyzed the genetic association of 79 SNPs of proteins associated with mineral metabolism disturbances with CKD in a cohort that includes 2, 445 CKD cases and 559 controls. Genotyping was performed with matrix assisted laser desorption ionizationtime of flight mass spectrometry. We used logistic regression models considering different genetic inheritance models to assess the association of the SNPs with the prevalence of CKD, adjusting for known risk factors. Eight SNPs (rs1126616, rs35068180, rs2238135, rs1800247, rs385564, rs4236, rs2248359, and rs1564858) were associated with CKD even after adjusting by sex, age and race. A model containing five of these SNPs (rs1126616, rs35068180, rs1800247, rs4236, and rs2248359), diabetes and hypertension showed better performance than models considering only clinical risk factors, significantly increasing the area under the curve of the model without polymorphisms. Furthermore, one of the SNPs (the rs2248359) showed an interaction with hypertension, being the risk genotype affecting only hypertensive patients. We conclude that 5 SNPs related to proteins implicated in mineral metabolism disturbances (Osteopontin, osteocalcin, matrix gla protein, matrix metalloprotease 3 and 24 hydroxylase) are associated to an increased risk of suffering CKD
Strategies to reengage patients lost to follow up in HIV care in high income countries, a scoping review
Background: Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90-90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods: A scoping review was done following Arksey & O'Malley's methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results: Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions: This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied
IMPACT-Global Hip Fracture Audit: Nosocomial infection, risk prediction and prognostication, minimum reporting standards and global collaborative audit. Lessons from an international multicentre study of 7,090 patients conducted in 14 nations during the COVID-19 pandemic
Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.
Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes
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