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

Atlas y libro rojo de la flora vascular amenazada de España: adenda 2010

Endemismo del centro-oeste y noroeste ibérico conocido de bastantes localidades, pero con área muy disyunta y con una ocupación real pequeña, con poblaciones fragmentadas constituidas por muy pocos individuos

Associations of dietary energy density with body composition and cardiometabolic risk in children with overweight and obesity: role of energy density calculations, under-reporting energy intake and physical activity

This study examined (1) the association of dietary energy density from solid (EDS) and solid plus liquids (EDSL) with adiposity and cardiometabolic risk factors (CRF) in children with overweight and obesity, (2) the effect of under-reporting on the mentioned associations and (3) whether the association between ED and body composition and CRF is influenced by levels of physical activity. In a cross-sectional design, 208 overweight and obese children (8-12-year-old; 111 boys) completed two non-consecutive 24 h recalls. ED was calculated using two different approaches: EDS and EDSL. Under-reporters were determined with the Goldberg method. Body composition, anthropometry and fasting blood sample measurements were performed. Moderate to vigorous physical activity (MVPA) was registered with accelerometers (7-d-register). Linear regressions were performed to evaluate the association of ED with the previously mentioned variables. Neither EDS nor EDSL were associated with body composition or CRF. However, when under-reporters were excluded, EDS was positively associated with BMI (P=0 019), body fat percentage (P=0 005), abdominal fat (P=0 008) and fat mass index (P=0 018), while EDSL was positively associated with body fat percentage (P=0 008) and fat mass index (P=0 026). When stratifying the group according to physical activity recommendations, the aforementioned associations were only maintained for non-compliers. Cluster analysis showed that the low-ED and high-MVPA group presented the healthiest profile for all adiposity and CRF. These findings could partly explain inconsistencies in literature, as we found that different ED calculations entail distinct results. Physical activity levels and excluding under-reporters greatly influence the associations between ED and adiposity in children with overweight and obesity.The research leading to these results has received funding from la Caixa Foundation and Triptolemos Foundation, the Ministry of Health (FIS PI081297), the Research Network on Preventative Activities and Health Promotion (RD06/0018/ 0038), the Henning and Johan Throne-Holst Foundation (F. B. O.), the Spanish Ministry of Education, Culture and Sport (FPU14/03329 to M. M.), the Spanish Ministry of Economy and Competitiveness (DEP2013-47540 and DEP2016-78377-R; BES-2014-068829 to C. C.-S.), Fondo de Investigacion Sanitaria del Instituto de Salud Carlos III (PI13/01335), Fondos Estructurales de la Union Europea (FEDER), Una manera de hacer Europa, the Spanish Ministry of Science and Innovation (RYC-2011-09011 to F. B. O.), the University of Granada, Plan Propio de Investigacion 2016, Excellence Actions: Units of Excellence, Unit of Excellence on Exercise and Health (UCEES), Programa de Captacion de Talento - UGR Fellows (L. G.-M.), the SAMID III network, RETICS (PN I +D+ I 2017-2021). This study has been partially funded by the University of Granada, Plan Propio de Investigacion 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucia, Consejeria de Conocimiento, Investigacion y Universidades and European Regional Development Fund (ERDF), reference SOMM17/6107/UGR. ISCIII-Sub-Directorate General for Research Assessment and Promotion, the European Regional Development Fund (RD16/ 0022), the EXERNET Research Network on Exercise and Health in Special Populations (DEP2005-00046/ACTI), and the University of the Basque Country (GIU14/21). J. M.-G. is supported by the Spanish Ministry of Education, Culture and Sport (FPU14/06837). J. H. M. is supported by the Spanish Ministry of Education, Culture and Sport (FPU15/02645)

The biota of the Upper Cretaceous site of Lo Hueco (Cuenca, Spain)

The Late Cretaceous (Campanian-Maastrichtian) fossil site of Lo Hueco was recently discovered close to the village of Fuentes (Cuenca, Spain) during the cutting of a little hill for installation of the railway of the Madrid-Levante high-speed train. To date, it has yielded a rich collection of well-preserved Cretaceous macrofossils, including plants, invertebrates, and vertebrates. The recovered fossil assemblage is mainly composed of plants, molluscs (bivalves and gastropods), actinopterygians and teleosteans fishes, amphibians, panpleurodiran (bothremydids) and pancryptodiran turtles, squamate lizards, eusuchian crocodyliforms, rhabdodontid ornithopods, theropods (mainly dromaeosaurids), and titanosaur sauropods. This assemblage was deposited in a near-coast continental muddy floodplain crossed by distributary sandy channels, exposed intermittently to brackish or marine and freshwater flooding as well as to partial or total desiccation events.The Konzentrat-Lagerstatt of Lo Hueco constitutes a singular accumulation of fossils representing individuals of some particular lineages of continental tetrapods, especially titanosaurs, eusuchians and bothremydid turtles. In the case of the titanosaurs, the site has yielded multiple partial skeletons in anatomical connection or with a low dispersion of their skeletal elements. A combination of new taxa, new records of taxa previously known in the Iberian Peninsula, and relatively common taxa in the European record compose the Lo Hueco biota. The particular conditions of the fossil site of Lo Hueco and the preliminary results indicate that the analysis of the geological context, the floral and faunal content, and the taphonomical features of the site provide elements that will be especially useful for reassess the evolutionary history of some lineages of European Late Cretaceous reptiles.Peer reviewe

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn''s disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of E-cadherin and ß-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology. © 2021 The Author

Randomised controlled trial of a prognostic assessment and management pathway to reduce the length of hospital stay in normotensive patients with acute pulmonary embolism

[Background] The length of hospital stay (LOS) for acute pulmonary embolism (PE) varies considerably. Whether the upfront use of a PE prognostic assessment and management pathway is effective in reducing the LOS remains unknown.[Methods] We conducted a randomised controlled trial of adults hospitalised for acute PE: patients were assigned either to a prognostic assessment and management pathway involving risk stratification followed by predefined criteria for mobilisation and discharge (intervention group) or to usual care (control group). The primary end-point was LOS. The secondary end-points were the cost of prognostic tests and of hospitalisation, and 30-day clinical outcomes.[Results] Of 500 patients who underwent randomisation, 498 were included in the modified intention-to-treat analysis. The median LOS was 4.0 days (interquartile range (IQR) 3.7–4.2 days) in the intervention group and 6.1 days (IQR 5.7–6.5 days) in the control group (p<0.001). The mean total cost of prognostic tests was EUR 174.76 in the intervention group, compared with EUR 233.12 in the control group (mean difference EUR −58.37, 95% CI EUR −84.34­ to −32.40). The mean total hospitalisation cost per patient was EUR 2085.66 in the intervention group, compared with EUR 3232.97 in the control group (mean difference EUR −1147.31, 95% CI EUR −1414.97­ to −879.65). No significant differences were observed in 30-day readmission (4.0% versus 4.8%), all-cause mortality (2.4% versus 2.0%) or PE-related mortality (0.8% versus 1.2%) rates.[Conclusions] The use of a prognostic assessment and management pathway was effective in reducing the LOS for acute PE.Peer reviewe

A clinically compatible drug-screening platform based on organotypic cultures identifies vulnerabilities to prevent and treat brain metastasis

We report a medium‐throughput drug‐screening platform (METPlatform) based on organotypic cultures that allows to evaluate inhibitors against metastases growing in situ. By applying this approach to the unmet clinical need of brain metastasis, we identified several vulnerabilities. Among them, a blood–brain barrier permeable HSP90 inhibitor showed high potency against mouse and human brain metastases at clinically relevant stages of the disease, including a novel model of local relapse after neurosurgery. Furthermore, in situ proteomic analysis applied to metastases treated with the chaperone inhibitor uncovered a novel molecular program in brain metastasis, which includes biomarkers of poor prognosis and actionable mechanisms of resistance. Our work validates METPlatform as a potent resource for metastasis research integrating drug‐screening and unbiased omic approaches that is compatible with human samples. Thus, this clinically relevant strategy is aimed to personalize the management of metastatic disease in the brain and elsewhere

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin β7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19