Evaluación neuropsicológica en niños y adolescentes con fenilcetonuria e hiperfenilalaninemia y su relación con los niveles de fenilalanina plasmática

P. 267-273Aunque, con tratamiento precoz, los pacientes con fenilcetonuria pueden presentar niveles de inteligencia normales, es importante optimizar el control dietético para mantener niveles de fenilalanina adecuados y poder desarrollar su potencial intelectual sin alteraciones en sus tareas diarias por déficits en las funciones ejecutivas. Se presenta una serie de 26 pacientes, diagnosticados y tratados precozmente, a quienes se realizó una evaluación psicométrica junto con determinaciones de fenilalanina a lo largo de su vida y en el momento de realización de los testsS

Levels of the Novel Endogenous Antagonist of Ghrelin Receptor, Liver-Enriched Antimicrobial Peptide-2, in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a debilitating, chronic, inflammatory, autoimmune disease associated with cachexia. The substitutive therapy of gut hormone ghrelin has been pointed at as a potential countermeasure for the management of metabolic and inflammatory complications in RA. The recent discovery of liver-expressed antimicrobial peptide 2 (LEAP2) as an endogenous inverse agonist/antagonist of the ghrelin receptor makes feasible the development of a more rational pharmacological approach. This work aimed to assess the serum LEAP2 levels, in a cohort of RA patients, in comparison with healthy individuals and determine its correlation with inflammatory parameters. LEAP2 levels were determined by a commercial ELISA kit, plasma C-reactive protein (CRP) levels were evaluated using immunoturbidimetry, and serum levels of inflammatory mediators, namely IL-6, IL-8, IL-1 , MIP1 , MCP1, and LCN2, were measured by XMap multiplex assay. LEAP2 serum levels were significantly increased in RA patients (n = 101) compared with control subjects (n = 26). Furthermore, the LEAP2 levels significantly correlated with CRP and inflammatory cytokines, but not with BMI. These data reveal LEAP2 as a new potential RA biomarker and indicated the pharmacological control of LEAP2 levels as a novel approach for the treatment of diseases with alterations on the ghrelin levels, such as rheumatoid cachexia

Afectación gastroduodenal como presentación inusual de la enfermedad de Crohn

It is relatively uncommon for Crohn’s disease to implicate the gastric and duodenal regions and occasionally it can cause pyloric stenosis, in which medical therapy may be ineffective and surgery might be required. We report two exceptional cases with prepyloric stenosis secondary to Crohn’s disease, aiming to emphasize the clinical suspicion and to describe the diagnostic imaging procedure and surgical treatments.Es relativamente infrecuente que la enfermedad de Crohs afecte al estomago y duodeno y ocasionalmente puede producir estenosis pilórica, en estas situaciones el tratamiento médico suele ser ineficaz y se requiere tratamiento quirúrgico. Se exponen dos casos clínicos excepcionales de estenosis prepilórica asociada a la enfermedad de Crohn, dirigidos a enfatizar en la sospecha clínica y describir el diagnóstico y el tratamiento quirúrgico

Using the Social-Local-Mobile App for Smoking Cessation in the SmokeFreeBrain Project: Protocol for a Randomized Controlled Trial

Background: Smoking is considered the main cause of preventable illness and early deaths worldwide. The treatment usually prescribed to people who wish to quit smoking is a multidisciplinary intervention, combining both psychological advice and pharmacological therapy, since the application of both strategies significantly increases the chance of success in a quit attempt. Objective: We present a study protocol of a 12-month randomized open-label parallel-group trial whose primary objective is to analyze the efficacy and efficiency of usual psychopharmacological therapy plus the Social-Local-Mobile app (intervention group) applied to the smoking cessation process compared with usual psychopharmacological therapy alone (control group). Methods: The target population consists of adult smokers (both male and female) attending the Smoking Cessation Unit at Virgen del Rocío University Hospital, Seville, Spain. Social-Local-Mobile is an innovative intervention based on mobile technologies and their capacity to trigger behavioral changes. The app is a complement to pharmacological therapies to quit smoking by providing personalized motivational messages, physical activity monitoring, lifestyle advice, and distractions (minigames) to help overcome cravings. Usual pharmacological therapy consists of bupropion (Zyntabac 150 mg) or varenicline (Champix 0.5 mg or 1 mg). The main outcomes will be (1) the smoking abstinence rate at 1 year measured by means of exhaled carbon monoxide and urinary cotinine tests, and (2) the result of the cost-effectiveness analysis, which will be expressed in terms of an incremental cost-effectiveness ratio. Secondary outcome measures will be (1) analysis of the safety of pharmacological therapy, (2) analysis of the health-related quality of life of patients, and (3) monitoring of healthy lifestyle and physical exercise habits. Results: Of 548 patients identified using the hospital’s electronic records system, we excluded 308 patients: 188 declined to participate and 120 did not meet the inclusion criteria. A total of 240 patients were enrolled: the control group (n=120) will receive usual psychopharmacological therapy, while the intervention group (n=120) will receive usual psychopharmacological therapy plus the So-Lo-Mo app. The project was approved for funding in June 2015. Enrollment started in October 2016 and was completed in October 2017. Data gathering was completed in November 2018, and data analysis is under way. The first results are expected to be submitted for publication in early 2019. Conclusions: Social networks and mobile technologies influence our daily lives and, therefore, may influence our smoking habits as well. As part of the SmokeFreeBrain H2020 European Commission project, this study aims at elucidating the potential role of these technologies when used as an extra aid to quit smoking

A Mobile Health Solution Complementing Psychopharmacology-Supported Smoking Cessation: Randomized Controlled Trial

Background: Smoking cessation is a persistent leading public health challenge. Mobile health (mHealth) solutions are emerging to improve smoking cessation treatments. Previous approaches have proposed supporting cessation with tailored motivational messages. Some managed to provide short-term improvements in smoking cessation. Yet, these approaches were either static in terms of personalization or human-based nonscalable solutions. Additionally, long-term effects were neither presented nor assessed in combination with existing psychopharmacological therapies. Objective: This study aimed to analyze the long-term efficacy of a mobile app supporting psychopharmacological therapy for smoking cessation and complementarily assess the involved innovative technology. Methods: A 12-month, randomized, open-label, parallel-group trial comparing smoking cessation rates was performed at Virgen del Rocío University Hospital in Seville (Spain). Smokers were randomly allocated to a control group (CG) receiving usual care (psychopharmacological treatment, n=120) or an intervention group (IG) receiving psychopharmacological treatment and using a mobile app providing artificial intelligence–generated and tailored smoking cessation support messages (n=120). The secondary objectives were to analyze health-related quality of life and monitor healthy lifestyle and physical exercise habits. Safety was assessed according to the presence of adverse events related to the pharmacological therapy. Per-protocol and intention-to-treat analyses were performed. Incomplete data and multinomial regression analyses were performed to assess the variables influencing participant cessation probability. The technical solution was assessed according to the precision of the tailored motivational smoking cessation messages and user engagement. Cessation and no cessation subgroups were compared using t tests. A voluntary satisfaction questionnaire was administered at the end of the intervention to all participants who completed the trial. Results: In the IG, abstinence was 2.75 times higher (adjusted OR 3.45, P=.01) in the per-protocol analysis and 2.15 times higher (adjusted OR 3.13, P=.002) in the intention-to-treat analysis. Lost data analysis and multinomial logistic models showed different patterns in participants who dropped out. Regarding safety, 14 of 120 (11.7%) IG participants and 13 of 120 (10.8%) CG participants had 19 and 23 adverse events, respectively (P=.84). None of the clinical secondary objective measures showed relevant differences between the groups. The system was able to learn and tailor messages for improved effectiveness in supporting smoking cessation but was unable to reduce the time between a message being sent and opened. In either case, there was no relevant difference between the cessation and no cessation subgroups. However, a significant difference was found in system engagement at 6 months (P=.04) but not in all subsequent months. High system appreciation was reported at the end of the study. Conclusions: The proposed mHealth solution complementing psychopharmacological therapy showed greater efficacy for achieving 1-year tobacco abstinence as compared with psychopharmacological therapy alone. It provides a basis for artificial intelligence–based future approaches. Trial Registration: ClinicalTrials.gov NCT03553173; https://clinicaltrials.gov/ct2/show/NCT03553173 International Registered Report Identifier (IRRID): RR2-10.2196/12464H2020 European Commission research and innovation program grant agreement 68112

HIV and HCV screening by non-infectious diseases physicians: can we improve testing and hidden infection rates?

BackgroundMissed opportunities for Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) testing remain high. We aimed to ascertain the knowledge of screening guidelines and attitudes of non-infectious disease (ID) hospital physicians and assess the impact of a 1-h session on screening rates and diagnoses.MethodsThis interventional study consisted of a 1-h training session on HIV and HCV epidemiology and testing guidelines for non-ID physicians. Pre-and post-session questionnaires compared the knowledge of the guidelines and attitudes toward screening before and after the session. Rates of screening and diagnoses were compared in three 6 months periods: before, immediately after, and 24 months ±4 after the session.ResultsA total of 345 physicians from 31 departments participated in these sessions. Before the session, 19.9% (28% medical, 8% surgical) and 17.9% (30% medical, 2.7% surgical) were aware of HIV and HCV testing guidelines, respectively. The willingness to routinely test increased from 5.6 to 22%, whereas not ordering tests decreased from 34.1 to 2.4%. HIV screening rates significantly increased by 20% after the session (7.7 vs. 9.3 tests per 103 patients; p < 0.001), and the effect persisted until the long-term period. The HIV diagnosis rate increased globally (3.6 vs. 5.2 HIV diagnoses per 105 patients; p = 0.157), mainly because of medical services (4.7 vs. 7.7 per 105 patients; p = 0.082). The HCV screening rate increased significantly immediately and in the long term only in medical services (15.7 and 13.6%, respectively). The new active HCV infection rates increased immediately and declined steeply thereafter.ConclusionA short session for non-ID physicians can improve HIV/HCV screening, increase diagnosis, and contribute to disease elimination

Innovación turística y desarrollo regional

Libro que se compila 14 capítulos asociados a las temáticas de innovación y desarrollo tecnológico en el sector turístico, emprendimiento y tecnologías emergentes, políticas estratégicas y tácticas para mejorar la competitividad en las empresas, políticas públicas y educación para el desarrollo regional y responsabilidad social ambientalBook that compiles 14 chapters associated to the themes of innovation and technological development in the tourism sector, entrepreneurship and emerging technologies, strategic and tactical policies to improve competitiveness in companies, public policies and education for regional development and environmental social responsibilityInnovación social como estrategia para el desarrollo de las poblaciones palafíticas de la ciénaga grande de santa marta mediante la oferta de productos turísticos / Gregoria Polo de Lobatón; José Luis Rosenstiehl Martínez; Daulis Lobatón Polo -- Uso de las tic para mejorar la competitividad turística en San Basilio de Palenque / Jesús Llerena Cabrera; Raúl José Martelo Gómez; David Franco Borré -- Plataforma web niu (nuevo, ideas y usados) / Néstor José Ocampo Ardila -- Posicionamiento estratégico del turismo urbano de eventos como atributo de la personalidad del espacio territorial de la ciudad de santa marta / Zuleidy María Ruíz Torres -- Identificación competitiva de la oferta exportadora de la región ariari para fortalecer el desarrollo social y económico en zonas de posconflicto basado en el comercio exterior y logística / Keyla Karina González Martínez -- Tecnologías integradas en gestión sostenible de operadores turísticos en zonas de posconflicto del departamento del meta / Carlos Hernán Cruz Castro; óscar Eduardo Sarmiento Saavedra -- Herramienta online de control de ingresos y facturación: una solución dinámica para las pequeñas y medianas empresas / Esmerlis Camargo Torres; Antonio José González Liñán; Marieth Orcasitas Peñaloza; Yerson Monroy Contreras -- Modelo de cadena productiva dinamizado a través de la educación y las estrategias TIC para el desarrollo regional sostenible en Risaralda / Beatriz Elena Franco Cárdenas; Patricia Henao Montoya; Marco Aurelio Aristizabal Valencia -- Evaluación físico - química de adhesivo de yuca (manihot esculenta) como alternativa comercial para la Orinoquia / Yarithza Molina Caro; Wilfran Hernán Cortes Conde -- Formulaciones nutracéuticas alimenticias para estilos de vida saludables / Daldo Araujo Vidal; Daniel Mendoza Cujia; Maresa Anaya de oro -- Competencias tecnológicas como estrategia formativa en los aprendices de gestión de redes de datos del SENA regional guajira / Carlos Antonio Salas Solano; Alejandro Jesús Osorio Amaya; Alda Pérez Campuzano; Duvan Andrés rondón bravo -- Uso y apropiación del computador como herramienta para las prácticas educativas de los docentes / Alda Pérez Campuzano; Carlos Antonio Salas Solano; Elkin Fuentes Jiménez; Kira Rodríguez Moscote -- El aviturismo como eje transformador de cultura ambiental y desarrollo sustentable / Lina María Gamarra Pineda; Néstor Alejandro Tascón Arias -- Huella ecológica (he), indicador de condición ambiental para evaluar la sostenibilidad en instituciones de educación (ie) / Cristian David Trujillo CardonaPrimera ediciónna169 página

The Lipopolysaccharide Core of Brucella abortus Acts as a Shield Against Innate Immunity Recognition

Innate immunity recognizes bacterial molecules bearing pathogen-associated molecular patterns to launch inflammatory responses leading to the activation of adaptive immunity. However, the lipopolysaccharide (LPS) of the gram-negative bacterium Brucella lacks a marked pathogen-associated molecular pattern, and it has been postulated that this delays the development of immunity, creating a gap that is critical for the bacterium to reach the intracellular replicative niche. We found that a B. abortus mutant in the wadC gene displayed a disrupted LPS core while keeping both the LPS O-polysaccharide and lipid A. In mice, the wadC mutant induced proinflammatory responses and was attenuated. In addition, it was sensitive to killing by non-immune serum and bactericidal peptides and did not multiply in dendritic cells being targeted to lysosomal compartments. In contrast to wild type B. abortus, the wadC mutant induced dendritic cell maturation and secretion of pro-inflammatory cytokines. All these properties were reproduced by the wadC mutant purified LPS in a TLR4-dependent manner. Moreover, the core-mutated LPS displayed an increased binding to MD-2, the TLR4 co-receptor leading to subsequent increase in intracellular signaling. Here we show that Brucella escapes recognition in early stages of infection by expressing a shield against recognition by innate immunity in its LPS core and identify a novel virulence mechanism in intracellular pathogenic gram-negative bacteria. These results also encourage for an improvement in the generation of novel bacterial vaccines

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality