Validation of the Spanish version of the Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire

The Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire (FHC-OHRQOL-Q) is an instrument designed specifically for parents and caregivers of patients with special needs that has not yet been applied in Spain. The aim of this study was to adapt it to Spanish and evaluate its reliability and validity in patients with intellectual disability (ID) treated under general anesthesia. The study was conducted in two different stages: a) cross-cultural adaptation of the original questionnaire, and b) cross-sectional study on 100 parents and caregivers who completed the piloted FHC-OHRQOL-Q. The patients were examined according to the WHO methodology. Dental treatments performed were recorded. Statistical tests were used to evaluate reliability (internal consistency) and validity (content, criterion, construct and discriminant) of the instrument. The mean age was 24 years (range=4-71 years). The most frequent causes of ID were psychomotor retardation (25%) and cerebral palsy (24%). The items most frequently answered by parents and caregivers were eating and nutrition problems (80%) and bad breath/taste (57%). Reliability (Cronbach?s alpha coefficient) was considered excellent (alpha=0.80-0.95). The analysis of the factorial validity yielded similar results to the original questionnaire. The high response rate of items (>96%) allowed content validity. Criterion validity was confirmed by a significant correlation with questions on oral health and oral well-being. Discriminant validity was demonstrated by the significant association of ?21.5 years of age with worse oral symptoms (p=0.034) and parental concerns (p=0.005), DMFT index ?3 with daily life problems (p=0.02), ?4 decayed teeth with daily life problems (p=0.001), and >2 dental extractions with oral symptoms (p=0.000), daily life problems (p=0.002) and parent´s perceptions (p=0.043). The FHC-OHRQOL-Q in Spanish is a reliable and valid instrument to apply in clinical practice to evaluate the impact of OHRQOL in mostly adult patients with ID, accessible to Spanish-speaking parents and caregivers

Synthesis of Degraded Limonoid Analogs as New Antibacterial Scaffolds againstStaphylococcus aureus

Staphylococcus aureusand methicillin-resistantStaphylococcus aureus(MRSA) have become serious infections in humans and ruminants.S. aureusstrains are showing rapid changes to develop resistance in traditional antibiotic-containing systems. In the continuous fierce fight against the emergent multi-drug resistant bacterial strains, straightforward and scalable synthetic procedures to produce new active molecules are in demand. Analysis of molecular properties points to degraded limonoids as promising candidates. In this article, we report a simple synthetic approach to obtain degraded limonoid analogs as scaffolds for new antibacterial molecules. The minimum inhibitory concentrations againstS. aureuswere evaluated for the stereoisomer mixtures by the broth microdilution method. Analysis of results showed that the acetylated derivatives were the most active of them all

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology

To ascertain the role of inflammation in the response to ocrelizumab in primary-progressive multiple sclerosis (PPMS).Multicenter prospective study including 69 patients with PPMS who initiated ocrelizumab treatment, classified according to baseline presence [Gd+, n=16] or absence [Gd-, n=53] of gadolinium-enhancing lesions in brain MRI. Ten Gd+ (62.5%) and 41 Gd- patients (77.4%) showed non-evidence of disease activity (NEDA) defined as no disability progression or new MRI lesions after 1 year of treatment. Blood immune cell subsets were characterized by flow cytometry, serum immunoglobulins by nephelometry, and serum neurofilament light-chains (sNfL) by SIMOA. Statistical analyses were corrected with the Bonferroni formula.More than 60% of patients reached NEDA after a year of treatment, regardless of their baseline characteristics. In Gd+ patients, it associated with a low repopulation rate of inflammatory B cells accompanied by a reduction of sNfL values 6 months after their first ocrelizumab dose. Patients in Gd- group also had low B cell numbers and sNfL values 6 months after initiating treatment, independent of their treatment response. In these patients, NEDA status was associated with a tolerogenic remodeling of the T and innate immune cell compartments, and with a clear increase of serum IgA levels.Baseline inflammation influences which immunological pathways predominate in patients with PPMS. Inflammatory B cells played a pivotal role in the Gd+ group and inflammatory T and innate immune cells in Gd- patients. B cell depletion can modulate both mechanisms.Copyright © 2022 Fernández-Velasco, Monreal, Kuhle, Meca-Lallana, Meca-Lallana, Izquierdo, Oreja-Guevara, Gascón-Giménez, Sainz de la Maza, Walo-Delgado, Lapuente-Suanzes, Maceski, Rodríguez-Martín, Roldán, Villarrubia, Saiz, Blanco, Diaz-Pérez, Valero-López, Diaz-Diaz, Aladro, Brieva, Íñiguez, González-Suárez, Rodríguez de Antonio, García-Domínguez, Sabin, Llufriu, Masjuan, Costa-Frossard and Villar

Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Elevated proinflammatory cytokines are associated with greater COVID-19 severity. We aimed to assess safety and efficacy of sarilumab, an interleukin-6 receptor inhibitor, in patients with severe (requiring supplemental oxygen by nasal cannula or face mask) or critical (requiring greater supplemental oxygen, mechanical ventilation, or extracorporeal support) COVID-19. Methods: We did a 60-day, randomised, double-blind, placebo-controlled, multinational phase 3 trial at 45 hospitals in Argentina, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Russia, and Spain. We included adults (≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and pneumonia, who required oxygen supplementation or intensive care. Patients were randomly assigned (2:2:1 with permuted blocks of five) to receive intravenous sarilumab 400 mg, sarilumab 200 mg, or placebo. Patients, care providers, outcome assessors, and investigators remained masked to assigned intervention throughout the course of the study. The primary endpoint was time to clinical improvement of two or more points (seven point scale ranging from 1 [death] to 7 [discharged from hospital]) in the modified intention-to-treat population. The key secondary endpoint was proportion of patients alive at day 29. Safety outcomes included adverse events and laboratory assessments. This study is registered with ClinicalTrials.gov, NCT04327388; EudraCT, 2020-001162-12; and WHO, U1111-1249-6021. Findings: Between March 28 and July 3, 2020, of 431 patients who were screened, 420 patients were randomly assigned and 416 received placebo (n=84 [20%]), sarilumab 200 mg (n=159 [38%]), or sarilumab 400 mg (n=173 [42%]). At day 29, no significant differences were seen in median time to an improvement of two or more points between placebo (12·0 days [95% CI 9·0 to 15·0]) and sarilumab 200 mg (10·0 days [9·0 to 12·0]; hazard ratio [HR] 1·03 [95% CI 0·75 to 1·40]; log-rank p=0·96) or sarilumab 400 mg (10·0 days [9·0 to 13·0]; HR 1·14 [95% CI 0·84 to 1·54]; log-rank p=0·34), or in proportions of patients alive (77 [92%] of 84 patients in the placebo group; 143 [90%] of 159 patients in the sarilumab 200 mg group; difference −1·7 [−9·3 to 5·8]; p=0·63 vs placebo; and 159 [92%] of 173 patients in the sarilumab 400 mg group; difference 0·2 [−6·9 to 7·4]; p=0·85 vs placebo). At day 29, there were numerical, non-significant survival differences between sarilumab 400 mg (88%) and placebo (79%; difference +8·9% [95% CI −7·7 to 25·5]; p=0·25) for patients who had critical disease. No unexpected safety signals were seen. The rates of treatment-emergent adverse events were 65% (55 of 84) in the placebo group, 65% (103 of 159) in the sarilumab 200 mg group, and 70% (121 of 173) in the sarilumab 400 mg group, and of those leading to death 11% (nine of 84) were in the placebo group, 11% (17 of 159) were in the sarilumab 200 mg group, and 10% (18 of 173) were in the sarilumab 400 mg group. Interpretation: This trial did not show efficacy of sarilumab in patients admitted to hospital with COVID-19 and receiving supplemental oxygen. Adequately powered trials of targeted immunomodulatory therapies assessing survival as a primary endpoint are suggested in patients with critical COVID-19. Funding: Sanofi and Regeneron Pharmaceuticals

Open borders in the nineteenth century : constructing the national, the citizen and the foreigner in South America

This working paper describes and explains the historical origins of the division between the national and the foreigner in South America. In the early nineteenth century, all the previously Spanish possessions in South America as well as Brazil achieved independence. With this new freedom, countries turned their attention to asserting their statehood through the delineation of three constitutive elements: government, territory and population. The new governments had to define who were going to be considered as nationals, citizens and foreigners, and the rights that pertained to each of these categories. These countries were all concerned with attracting new settlers and very early on introduced constitutional provisions on open borders and equal treatment for foreigners. White, male Europeans were the principal addresses of open borders provisions in an effort to entice them to settle in territories presented as empty to the exclusion of indigenous groups, bring new industries, and contribute to the whitening of mixed race populations. Whilst weak statehood came with independence, forming nations was a much longer process and States used migration and citizenship policies as tools to define nationhood

Discovering HIV related information by means of association rules and machine learning

Acquired immunodeficiency syndrome (AIDS) is still one of the main health problems worldwide. It is therefore essential to keep making progress in improving the prognosis and quality of life of affected patients. One way to advance along this pathway is to uncover connections between other disorders associated with HIV/AIDS-so that they can be anticipated and possibly mitigated. We propose to achieve this by using Association Rules (ARs). They allow us to represent the dependencies between a number of diseases and other specific diseases. However, classical techniques systematically generate every AR meeting some minimal conditions on data frequency, hence generating a vast amount of uninteresting ARs, which need to be filtered out. The lack of manually annotated ARs has favored unsupervised filtering, even though they produce limited results. In this paper, we propose a semi-supervised system, able to identify relevant ARs among HIV-related diseases with a minimal amount of annotated training data. Our system has been able to extract a good number of relationships between HIV-related diseases that have been previously detected in the literature but are scattered and are often little known. Furthermore, a number of plausible new relationships have shown up which deserve further investigation by qualified medical experts

Operative definition of active and healthy ageing (AHA): Meeting report. Montpellier October 20-21, 2014

The broad concept of Active and Healthy Ageing was proposed by WHO as the process of optimizing opportunities for health to enhance quality of life as people age. It applies to both individuals and population groups. A universal active and healthy ageing definition is not available and may differ depending on the purpose of the definition and/or the questions raised. The European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) has had a major impact but a definition of Active and Healthy Ageing is urgently needed. A meeting was organised in Montpellier October 20-21, 2014 as the annual conference of the EIP on AHA Reference Site MACVIA-LR (contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc Roussillon). The goal of the meeting was to propose an operational definition of Active and Healthy Ageing as well as tools that may be used for this definition. The current paper provides a summary of the plenary presentations that were given during the meeting