Actividad antifúngica y antitoxigénica in vitro y en alimentos de bacterias ácido lácticas

El desarrollo de hongos en materias primas, alimentos y piensos puede ser responsable de pérdidas económicas considerables por disminuir la calidad y reducir la vida media de todos ellos. Además, algunos hongos pueden producir compuestos potencialmente tóxicos, lo que supone un problema de seguridad alimentaria para los consumidores. La bioconservación es un concepto que se refiere al empleo de microorganismos o sus productos metabólicos en los alimentos, para inhibir el crecimiento o destruir microorganismos no deseados, con el objetivo de mejorar la seguridad, conservar la calidad y extender la vida útil de los productos alimenticios. La presente Tesis Doctoral tiene por objeto el estudio de la actividad antifúngica de bacterias ácido lácticas (BAL) frente a hongos productores de micotoxinas pertenecientes a los géneros Aspergillus, Penicillium y Fusarium. Para tal efecto, se realizaron fermentaciones en caldo MRS, suero de leche y masa madre panaria, y se determinaron los valores de concentración mínima fungicida, a efectos de comparar el potencial antifúngico. En base a estos primeros datos, se planteó la necesidad de desarrollar estrategias basadas en el uso de las BAL más activas como cultivos iniciadores de fermentación en el propio alimento o bien empleando el caldo fermentado libre o no de células como ingrediente, de manera que proporcionaran valores positivos en cuanto a el aumentar la vida útil de los alimentos y la reducción de la presencia de micotoxinas. Los resultados obtenidos reflejan una eficacia de las BAL y los medios fermentados como conservantes de origen natural frente a P. expansum en pan, con valores medios equivalentes o ligeramente superiores a los que presentan los conservantes clásicos ampliamente utilizados por la industria alimentaria, como es el caso del propianato de calcio. Por otra parte, la pulverización del caldo MRS fermentado por L. plantarum CECT 749 retrasó el crecimiento de A. flavus en maíz y F. verticillioides en mazorca en varios días frente al blanco. Dicho tratamiento evidenció una muy importante reducción en la producción de AFB1 por A. flavus en maíz, y por F. verticillioides en mazorcas de maíz durante el almacenamiento. Como efectos beneficiosos adicionales, cabe decir que la digestión gastrointestinal de pan contaminado con OTA y previamente tratado con diversos inóculos de BAL mostraron una marcada reducción de la bioaccesibilidad de la micotoxina en los diferentes compartimentos digestivos in vitro. Y que la fermentación del suero de leche con cepas de L. plantarum mostraron un aumento de la capacidad antioxidante, un mayor porcentaje de la actividad inhibitoria de la enzima convertidora de la angiotensina y un incremento de la capacidad de quelación del hierro.The development of fungi in raw materials, food and feed can be responsible for considerable economic losses by decreasing quality and reducing the shelf life of all of them. In addition, some fungi can produce potentially toxic compounds, posing a food safety problem for consumers. Biopreservation is a concept that refers to the use of microorganisms or their metabolic products in food, to inhibit the growth or destroy unwanted microorganisms, with the aim of improving safety, preserving quality and extending the shelf life of food products. The purpose of this Doctoral Thesis is to study the antifungal activity of lactic acid bacteria (LAB) against fungi that produce mycotoxins belonging to the genera Aspergillus, Penicillium and Fusarium. For this purpose, fermentations were carried out in MRS broth, whey and panary sourdough, and the minimum fungicidal concentration values were determined, in order to compare the antifungal potential. Based on these first data, the need to develop strategies based on the use of the most active LAB as fermentation starter cultures in the food itself or using the cell-free or non-cell-free fermented broth as an ingredient was raised, in order to provide positive values in terms of increasing the shelf life of food and reducing the presence of mycotoxins. The results obtained reflect the efficacy of LAB and the fermented media as preservatives of natural origin against P. expansum in bread, with mean values equivalent to or slightly higher than those of the classic preservatives widely used by the food industry, such as case of calcium propionate. On the other hand, the spraying of the MRS broth fermented by L. plantarum CECT 749 delayed the growth of A. flavus in corn and F. verticillioides on the cob for several days against white. This treatment evidenced a very important reduction in the production of AFB1 by A. flavus in corn, and by F. verticillioides in corn cobs during storage. As additional beneficial effects, it can be said that the gastrointestinal digestion of bread contaminated with OTA and previously treated with various LAB inoculum showed a marked reduction in the bioavailability of mycotoxin in the different digestive compartments in vitro. And that the fermentation of the whey with L. plantarum strains showed an increase in the antioxidant capacity, a higher percentage of the inhibitory activity of the angiotensin-converting enzyme and an increase in the chelation capacity of iron

A personalized intervention to prevent depression in primary care: cost-effectiveness study nested into a clustered randomized trial

Abstract Background: Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care. Methods: Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months.This work was supported by grants from the Spanish Ministry of Health, the Institute of Health Carlos III (ISCIII) and the European Regional Development Fund (ERDF) ’A way to build Europe’(grant references PS09/02272, PS09/02147, PS09/01095, PS09/00849 and PS09/00461); the Andalusian Council of Health (grant reference PI-0569-2010); the Spanish Network of Primary Care Research ’redIAPP’ (RD06/0018, RD12/0005/0001); the ’Aragón group’ (RD06/0018/0020, RD12/0005/0006); the ’Bizkaya group’ (RD06/0018/0018, RD12/0005/0010); the Castilla-León Group (RD06/0018/0027); the Mental Health (SJD) Barcelona Group (RD06/0018/0017, RD12/0005/0008); and the Mental-Health, Services and Primary Care (SAMSERAP) MálagaGroup (RD06/0018/0039, RD12/0005/0005)

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

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

Inhibitory Activity of Shrimp Waste Extracts on Fungal and Oomycete Plant Pathogens

(1) Background: This study was aimed at determining the in vitro inhibitory effect of new natural substances obtained by minimal processing from shrimp wastes on fungi and oomycetes in the genera Alternaria, Colletotrichum, Fusarium, Penicillium, Plenodomus and Phytophthora; the effectiveness of the substance with the highest in vitro activity in preventing citrus and apple fruit rot incited by P. digitatum and P. expansum, respectively, was also evaluated. (2) Methods: The four tested substances, water-extract, EtOAc-extract, MetOH-extract and nitric-extract, were analyzed by HPLC-ESI-MS-TOF; in vitro preliminary tests were carried out to determine the minimal inhibitory/fungicidal concentrations (MIC and MFC, respectively) of the raw dry powder, EtOAc-extract, MetOH-extract and nitric-extract for each pathogen. (3) Results: in the agar-diffusion-assay, nitric-extract showed an inhibitory effect on all pathogens, at all concentrations tested (100, 75, 50 and 25%); the maximum activity was on Plenodomus tracheiphilus, C. gloeosporioides and Ph. nicotianae; the diameters of inhibition halos were directly proportional to the extract concentration; values of MIC and MFC of this extract for all pathogens ranged from 2 to 3.5%; the highest concentrations (50 to 100%) tested in vivo were effective in preventing citrus and apple fruit molds. (4) Conclusions: This study contributes to the search for natural and ecofriendly substances for the control of pre- and post-harvest plant pathogens

Inhibitory Activity of Shrimp Waste Extracts on Fungal and Oomycete Plant Pathogens

(1) Background: This study was aimed at determining the in vitro inhibitory effect of new natural substances obtained by minimal processing from shrimp wastes on fungi and oomycetes in the genera Alternaria, Colletotrichum, Fusarium, Penicillium, Plenodomus and Phytophthora; the effectiveness of the substance with the highest in vitro activity in preventing citrus and apple fruit rot incited by P. digitatum and P. expansum, respectively, was also evaluated. (2) Methods: The four tested substances, water-extract, EtOAc-extract, MetOH-extract and nitric-extract, were analyzed by HPLC-ESI-MS-TOF; in vitro preliminary tests were carried out to determine the minimal inhibitory/fungicidal concentrations (MIC and MFC, respectively) of the raw dry powder, EtOAc-extract, MetOH-extract and nitric-extract for each pathogen. (3) Results: in the agar-diffusion-assay, nitric-extract showed an inhibitory effect on all pathogens, at all concentrations tested (100, 75, 50 and 25%); the maximum activity was on Plenodomus tracheiphilus, C. gloeosporioides and Ph. nicotianae; the diameters of inhibition halos were directly proportional to the extract concentration; values of MIC and MFC of this extract for all pathogens ranged from 2 to 3.5%; the highest concentrations (50 to 100%) tested in vivo were effective in preventing citrus and apple fruit molds. (4) Conclusions: This study contributes to the search for natural and ecofriendly substances for the control of pre- and post-harvest plant pathogens

A personalized intervention to prevent depression in primary care: cost-effectiveness study nested into a clustered randomized trial.

Depression is viewed as a major and increasing public health issue, as it causes high distress in the people experiencing it and considerable financial costs to society. Efforts are being made to reduce this burden by preventing depression. A critical component of this strategy is the ability to assess the individual level and profile of risk for the development of major depression. This paper presents the cost-effectiveness of a personalized intervention based on the risk of developing depression carried out in primary care, compared with usual care. Cost-effectiveness analyses are nested within a multicentre, clustered, randomized controlled trial of a personalized intervention to prevent depression. The study was carried out in 70 primary care centres from seven cities in Spain. Two general practitioners (GPs) were randomly sampled from those prepared to participate in each centre (i.e. 140 GPs), and 3326 participants consented and were eligible to participate. The intervention included the GP communicating to the patient his/her individual risk for depression and personal risk factors and the construction by both GPs and patients of a psychosocial programme tailored to prevent depression. In addition, GPs carried out measures to activate and empower the patients, who also received a leaflet about preventing depression. GPs were trained in a 10- to 15-h workshop. Costs were measured from a societal and National Health care perspective. Qualityadjustedlife years were assessed using the EuroQOL five dimensions questionnaire. The time horizon was 18 months. With a willingness-to-pay threshold of €10,000 (£8568) the probability of cost-effectiveness oscillated from 83% (societal perspective) to 89% (health perspective). If the threshold was increased to €30,000 (£25,704), the probability of being considered cost-effective was 94% (societal perspective) and 96%, respectively (health perspective). The sensitivity analysis confirmed these results. Compared with usual care, an intervention based on personal predictors of risk of depression implemented by GPs is a cost-effective strategy to prevent depression. This type of personalized intervention in primary care should be further developed and evaluated. ClinicalTrials.gov, NCT01151982. Registered on June 29, 2010