From Ethnomedicine to Plant Biotechnology and Machine Learning: The Valorization of the Medicinal Plant Bryophyllum sp.

The subgenus Bryophyllum includes about 25 plant species native to Madagascar, and is widely used in traditional medicine worldwide. Different formulations from Bryophyllum have been employed for the treatment of several ailments, including infections, gynecological disorders, and chronic diseases, such as diabetes, neurological and neoplastic diseases. Two major families of secondary metabolites have been reported as responsible for these bioactivities: phenolic compounds and bufadienolides. These compounds are found in limited amounts in plants because they are biosynthesized in response to different biotic and abiotic stresses. Therefore, novel approaches should be undertaken with the aim of achieving the phytochemical valorization of Bryophyllum sp., allowing a sustainable production that prevents from a massive exploitation of wild plant resources. This review focuses on the study of phytoconstituents reported on Bryophyllum sp.; the application of plant tissue culture methodology as a reliable tool for the valorization of bioactive compounds; and the application of machine learning technology to model and optimize the full phytochemical potential of Bryophyllum sp. As a result, Bryophyllum species can be considered as a promising source of plant bioactive compounds, with enormous antioxidant and anticancer potential, which could be used for their large-scale biotechnological exploitation in cosmetic, food, and pharmaceutical industriesThis research was funded by Xunta de Galicia through “Red de Uso Sostenible de los Recursos Naturales y Agroalimentarios” (REDUSO, grant number ED431D 2017/18) and “Cluster of Agricultural Research and Development” (CITACA Strategic Partnership, gran numbered ED431E 2018/07). The authors acknowledge the FPU grant awarded to Pascual García-Pérez from the Spanish Ministry of Education (grant number FPU15/04849)S

Machine Learning Technology Reveals the Concealed Interactions of Phytohormones on Medicinal Plant In Vitro Organogenesis

Organogenesis constitutes the biological feature driving plant in vitro regeneration, in which the role of plant hormones is crucial. The use of machine learning (ML) technology stands out as a novel approach to characterize the combined role of two phytohormones, the auxin indoleacetic acid (IAA) and the cytokinin 6-benzylaminopurine (BAP), on the in vitro organogenesis of unexploited medicinal plants from the Bryophyllum subgenus. The predictive model generated by neurofuzzy logic, a combination of artificial neural networks (ANNs) and fuzzy logic algorithms, was able to reveal the critical factors affecting such multifactorial process over the experimental dataset collected. The rules obtained along with the model allowed to decipher that BAP had a pleiotropic effect on the Bryophyllum spp., as it caused different organogenetic responses depending on its concentration and the genotype, including direct and indirect shoot organogenesis and callus formation. On the contrary, IAA showed an inhibiting role, restricted to indirect shoot regeneration. In this work, neurofuzzy logic emerged as a cutting-edge method to characterize the mechanism of action of two phytohormones, leading to the optimization of plant tissue culture protocols with high large-scale biotechnological applicabilityThe authors acknowledge the FPU grant awarded to Pascual García-Pérez from the Spanish Ministry of Education (grant number FPU15/04849)S

Neurofuzzy logic predicts a fine-tuning metabolic reprogramming on elicited Bryophyllum PCSCs guided by salicylic acid

Novel approaches to the characterization of medicinal plants as biofactories have lately increased in the field of biotechnology. In this work, a multifaceted approach based on plant tissue culture, metabolomics, and machine learning was applied to decipher and further characterize the biosynthesis of phenolic compounds by eliciting cell suspension cultures from medicinal plants belonging to the Bryophyllum subgenus. The application of untargeted metabolomics provided a total of 460 phenolic compounds. The biosynthesis of 164 of them was significantly modulated by elicitation. The application of neurofuzzy logic as a machine learning tool allowed for deciphering the critical factors involved in the response to elicitation, predicting their influence and interactions on plant cell growth and the biosynthesis of several polyphenols subfamilies. The results indicate that salicylic acid plays a definitive genotype-dependent role in the elicitation of Bryophyllum cell cultures, while methyl jasmonate was revealed as a secondary factor. The knowledge provided by this approach opens a wide perspective on the research of medicinal plants and facilitates their biotechnological exploitation as biofactories in the food, cosmetic and pharmaceutical fields.Xunta de Galicia | Ref. ED431E 2018/07Xunta de Galicia | Ref. ED431D2017/1

Impact of the implementation of a telemedicine program on patients diagnosed with asthma.

Background: Asthma is one of the most common respiratory ailments worldwide. Despite broad understanding of the illness and of the available therapeutic options for it, patients with serious asthma suffer poor monitoring of their illness in 50% of cases. Aim: To assess the impact of the implementation of a mobile application (ESTOI) to control asthma in patients diagnosed with the illness, their adherence to treatment, and their perceived quality of life. Methodology: Randomized clinical trial with 52 weeks' follow-up of patients with asthma seen in a specialized hospital for their treatment in Spain. Some 108 included patients will be divided into two groups. The intervention group will undergo more exhaustive follow-up than normal, including access to the ESTOI application, which will have various categories of attention: control of symptoms, health recommendations, current treatment and personalized action plan, PEF record, nutritional plan, and chat access with a medical team. The asthma control questionnaire ACT is the main assessment variable. Other variables to be studied include an adherence test for the use of inhalers (TAI), the number of exacerbations, maximum exhalation flow, exhaled nitric oxide test, hospital anxiety and depression scale, asthma quality-of-life questionnaire, forced spirometry parameters (FVC, FEV1, and PBD), and analytic parameters (eosinophilia and IGE). The data will be collected during outpatient visits. Trial registration: This trial has registered at ClinicalTrials.gov (Identifier: NCT06116292)

Trabajo agrario y condiciones de salud

Se presentan los resultados  alcanzados del Proyecto de Extensión  “Trabajo agrario y condiciones de salud. Una falsa antinomia: trabajar para vivir o estar sano para trabajar”, actualmente en desarrollo. Aborda un área de vacancia de conocimientos constituido por el eje conceptual  salud - trabajo agrario – ambiente. Pretende conocer para transformar las condiciones de vida de esa población, además de fortalecer  desde  la Universidad un área de trabajo interdisciplinario e intersectorial dedicado a desarrollar acciones de sensibilización, divulgación y formación continua en la problemática de la salud rural.  La propuesta fue elaborada  a partir de una demanda de cinco organizaciones sociales de la localidad de Arana (La Plata. Buenos Aires. Argentina), preocupadas por las enfermedades recurrentes que afectan a los y las trabajadoras rurales. En su formulación participaron estudiantes, graduados y docentes de las siguientes Facultades de la UNLP: Humanidades y Ciencias de la Educación, Ciencias Exactas, Psicología y Ciencias Médicas. Fue subsidiado por la UNLP (2012) constituyéndose  la Facultad de Trabajo Social como  Unidad Ejecutora del mismo.  Este proyecto está dirigido a una población de 80 trabajadores rurales  y sus familias, vulnerada en sus derechos fundamentales por una triple estigmatización: ser migrante, precarizada y pobre. Profundiza un proceso de intervención llevado a cabo por la Cátedra Libre de Salud y Derechos Humanos de la Facultad de Ciencias Exactas  que durante el 2010 capacitó a trabajadores rurales en temáticas vinculadas a la salud, tales como: microorganismos patógenos y sustancias tóxicas, prevención de enfermedades y aproximaciones a los daños producidos por agro tóxicos. La propuesta en curso, está en la tarea de desnaturalizar la enfermedad padecida por las y los trabajadores rurales,  introduciendo la noción de salud  como  proceso determinado  por las relaciones de clase, género y etnia-cultura.  Sostiene que la desigualdad social produce que los sujetos sanen, enfermen o mueran de un modo similarmente desigual a como están distribuida la riqueza en una sociedad. El proceso de intervención comprende la realización de un relevamiento socio-sanitario ejecutado por los  trabajadores, plenarios con las organizaciones participantes, talleres de formación de promotores rurales,  realización de jornadas de salud para la realización de estudios oftalmológicos y hematológicos  realizados con la capacidad instalada y los recursos humanos de la UNLP.  La difusión de hallazgos y presentación de informes a los sectores involucrados, constituirá un aporte a la formulación de políticas públicas  que aborden sistemáticamente la problemática del trabajo rural y la salud de su gente.

The Response to Biologics is Better in Patients with Severe Asthma Than in Patients with Asthma–COPD Overlap Syndrome

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma-COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with >= 1 exacerbation and >= 1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of controlled patients (with no exacerbations, no need for corticosteroids and ACT >= 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-gamma-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18-20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50-0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66-0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20-22%] vs. 14% [95% CI 13-16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM

Allogeneic Stem Cell Transplantation in Mature T Cell and Natural Killer/T Neoplasias: A Registry Study from Spanish GETH/GELTAMO Centers

Despite advances in understanding the biology of mature T and natural killer (NK)/T cell neoplasia, current therapies, even the most innovative ones, are still far from ensuring its cure. The only treatment to date that has been shown to control aggressive T cell neoplasms in the long term is allogeneic stem cell transplantation (alloSCT). We aim to report the results of alloSCT for advanced mature T and NK/T neoplasias performed in centers from our national GELTAMO/GETH (Grupo Español de Linfoma y Trasplante de Médula Ósea/Grupo Español de Trasplante Hematopoyético y Terapia Celular) over the past 25 years. As a secondary objective, we analyzed the results of alloSCT from haploidentical donors. We performed a retrospective analysis of all patients who received an alloSCT in Spanish centers (n = 201) from September 1995 to August 2018. The 2-year overall survival (OS) and disease-free survival (DFS) were 65.5% and 58.2%, respectively. The univariate for OS and DFS showed statistically different hazard ratios for conditioning intensity, response pre-alloSCT, comorbidity index, donor/receptor cytomegalovirus status and Eastern Cooperative Oncology Group (ECOG) pre-alloSCT, but only a better ECOG pre-alloSCT remained significant in the multivariate analysis. There was an increased incidence of relapse in those patients who did not develop chronic graft-versus-host disease (GVHD) and an increased risk of death in those developing moderate to severe acute GVHD. The 1-year nonrelapse mortality was 21.9% and was mainly due to GVHD (30%) and bacterial infections (17%). When comparing unrelated donors with haploidentical donors, we found similar results in terms of OS and DFS. There was, however, a reduction of acute GVHD in the haploidentical group (P = .04) and trend to a reduction of chronic GVHD. In conclusion, alloSCT is the only curative option for most aggressive T cell neoplasias. Haploidentical donors offer similar results to related donors in terms of survival with a reduction of acute GVHD

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry

Background: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response