Fumigant Toxicity in Myzus persicae Sulzer (Hemiptera: Aphididae): Controlled Release of (E)-anethole from Microspheres

(E)-anethole is a phenylpropanoid that is the main compound found in the essential oils (EOs) of anise and fennel seeds, and either fumigant or direct contact activity of this compound has been demonstrated against aphids and stored product pests. In this work, solid microspheres were prepared by three methods—oil emulsion entrapment, spray-drying, and complexed with β-cyclodextrin. Fumigation activity of each microsphere preparation was tested against the green peach aphid, Myzus persicae Sulzer (Hemiptera: Aphididae), on pepper leaves. The best insecticidal activity was with (E)-anethole encapsulated in oil emulsion beads and introduced to aphids as a vapour over 24 h, with an LC50 of 0.415 μL/L compared to 0.336 μL/L of vapors from free (E)-anethole. Scanning electron microscopy of the beads revealed a compact surface with low porosity that produced a controlled release of the bioactive for more than 21 d, whilst most of the volatile was evaporated within two days if applied unformulated. Spray drying gave spherical particles with the greatest encapsulated yield (73%) of 6.15 g of (E)-anethole incorporated per 100 g of powder. Further work will be done on improving the formulation methods and testing the solid microspheres in all aphid stages scaling up the experimental assay. It is foreseen that nanotechnology will play a role in future developments of low risk plant protection product

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

Irisin as a Novel Biomarker of Subclinical Atherosclerosis in Severe Obesity

Severe obesity (SO) can accelerate atherosclerosis and the onset of acute cardiovascular events. The diagnosis of atherosclerosis in the context of a high body mass index (BMI) can be challenging, making the identification of biomarkers clinically relevant. We aimed to assess the usefulness of irisin as a biomarker for subclinical atherosclerosis in participants with SO. This prospective observational study included 61 participants undergoing bariatric surgery for SO, defined as a BMI >40 kg/m2 or >35 kg/m2 with at least one comorbidity. Atherosclerotic plaques were detected by ultrasound. Plasma samples were obtained 1 month before and at 6 and 12 months after bariatric surgery to measure irisin by ELISA. Additionally, subcutaneous samples of adipose tissue were taken and genotyped to identify irisin polymorphism rs3480. Irisin levels were positively correlated with BMI (r = 0.23, p = 0.0064), negatively correlated with atheroma-related parameters (e.g., carotid intima-media thickness), and lower in subjects with atheroma (p < 0.0002). Irisin also showed good overall accuracy for discriminating plaque presence (AUC, 0.81; 95% CI, 0.6956–0.9156). However, the rs3480 polymorphism correlated with neither the irisin levels nor the presence of atheromas. Iirisin could identify subclinical atherosclerosis in SO and might facilitate clinical diagnosis

raw data microRNA_Carmona-Maurici.xlsx

Raw data for human plasma miRNA screening and validation</p

Guideline Adherence in Outpatient Clinics for Chronic Obstructive Pulmonary Disease: Results from a Clinical Audit.

Journal ArticleOBJECTIVES Previous clinical audits of COPD have provided relevant information about medical intervention in exacerbation admissions. The present study aims to evaluate adherence to current guidelines in COPD through a clinical audit. METHODS This is a pilot clinical audit performed in hospital outpatient respiratory clinics in Andalusia, Spain (eight provinces with more than 8 million inhabitants), including 9 centers (20% of the public centers in the area) between 2013 and 2014. Cases with an established diagnosis of COPD based on risk factors, clinical symptoms, and a post-bronchodilator FEV1/FVC ratio of less than 0.70 were deemed eligible. The performance of the outpatient clinics was benchmarked against three guidance documents available at the time of the audit. The appropriateness of the performance was categorized as excellent (>80%), good (60-80%), adequate (40-59%), inadequate (20-39%), and highly inadequate (<20%). RESULTS During the audit, 621 clinical records were audited. Adherence to the different guidelines presented a considerable variability among the different participating hospitals, with an excellent or good adherence for symptom recording, MRC or CAT use, smoking status evaluation, spirometry, or bronchodilation therapy. The most outstanding areas for improvement were the use of the BODE index, the monitoring of treatments, the determination of alpha1-antitrypsin, the performance of exercise testing, and vaccination recommendations. CONCLUSIONS The present study reflects the situation of clinical care for COPD patients in specialized secondary care outpatient clinics. Adherence to clinical guidelines shows considerable variability in outpatient clinics managing COPD patients, and some aspects of the clinical care can clearly be improved.This study was financially supported by an unrestricted grant from Laboratorios Menarini, SA (Barcelona, Spain).Ye

Seasonal variability in clinical care of COPD outpatients: results from the Andalusian COPD audit

OBJECTIVES: Clinical practice in chronic obstructive pulmonary disease (COPD) can be influenced by weather variability throughout the year. To explore the hypothesis of seasonal variability in clinical practice, the present study analyzes the results of the 2013-2014 Andalusian COPD audit with regard to changes in clinical practice according to the different seasons. METHODS: The Andalusian COPD audit was a pilot clinical project conducted from October 2013 to September 2014 in outpatient respiratory clinics of hospitals in Andalusia, Spain (8 provinces with more than 8 million inhabitants) with retrospective data gathering. For the present analysis, astronomical seasons in the Northern Hemisphere were used as reference. Bivariate associations between the different COPD guidelines and the clinical practice changes over the seasons were explored by using binomial multivariate logistic regression analysis with age, sex, Charlson comorbidity index, type of hospital, and COPD severity by forced expiratory volume in 1 second as covariates, and were expressed as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: The Andalusian COPD audit included 621 clinical records from 9 hospitals. After adjusting for covariates, only inhaler device satisfaction evaluation was found to significantly differ according to the seasons with an increase in winter (OR, 3.460; 95% CI, 1.469-8.151), spring (OR, 4.215; 95% CI, 1.814-9.793), and summer (OR, 3.371; 95% CI, 1.391-8.169) compared to that in autumn. The rest of the observed differences were not significant after adjusting for covariates. However, compliance with evaluating inhaler satisfaction was low. CONCLUSION: The various aspects of clinical practice for COPD care were found to be quite homogeneous throughout the year for the variables evaluated. Inhaler satisfaction evaluation, however, presented some significant variation during the year. Inhaler device satisfaction should be evaluated during all clinical visits throughout the year for improved COPD management.This study was funded by an unrestricted grant from Menarini, SpainYe

Midkine rewires the melanoma microenvironment toward a tolerogenic and immune-resistant state.

An open question in aggressive cancers such as melanoma is how malignant cells can shift the immune system to pro-tumorigenic functions. Here we identify midkine (MDK) as a melanoma-secreted driver of an inflamed, but immune evasive, microenvironment that defines poor patient prognosis and resistance to immune checkpoint blockade. Mechanistically, MDK was found to control the transcriptome of melanoma cells, allowing for coordinated activation of nuclear factor-κB and downregulation of interferon-associated pathways. The resulting MDK-modulated secretome educated macrophages towards tolerant phenotypes that promoted CD8+ T cell dysfunction. In contrast, genetic targeting of MDK sensitized melanoma cells to anti-PD-1/anti-PD-L1 treatment. Emphasizing the translational relevance of these findings, the expression profile of MDK-depleted tumors was enriched in key indicators of a good response to immune checkpoint blockers in independent patient cohorts. Together, these data reveal that MDK acts as an internal modulator of autocrine and paracrine signals that maintain immune suppression in aggressive melanomas.We thank the colleagues at the CNIO Melanoma Group, as well as those at the laboratories of H. Peinado and Manuel V. (CNIO), for help and support, I. Blanco, S. Ruiz, V. Granda, S. Rueda (CNIO) and the Animal Facility, Histopathological Unit, Confocal Microscopy Unit and Crystallography and Protein Engineering Unit of CNIO for assistance with the mouse colonies and histopathological and protein analyses, and D. Sancho (CNIC) for the B16-OVAGFP cells and OT-I mouse strain, and for scientific guidance. P. Turko (University of Zurich) provided advice on the statistical analyses of tissue microarrays. We also thank the donors and the Biobank Hospital Universitario Puerta De Hierro Majadahonda (HUPHM)/Instituto De Investigacion Sanitaria Puerta De Hierro-Segovia De Arana (IDIPHISA) (PT17/0015/0020 in the Spanish National Biobanks Network) for the human specimens used in this study. M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (SAF2017-89533-R), Team Science and Established Investigator awards by the Melanoma Research Alliance, and grants from Worldwide Cancer Research and Fundacion 'La Caixa' Health Research 2019. M.S.S., P.O.-R. and J.L.R.-P. are funded by a collaborative grant from the Asociacion Espanola Contra el Cancer (AECC). D.O. is funded by grants from the Spanish Ministry of Health (AES-PIS PI18/1057) and 'Fundacion BBVA-Becas Leonardo a Investigadores y Creadores Culturales 2018'. D.C.-W. was a recipient of a predoctoral fellowship from Fundacion 'La Caixa' and is currently funded by the AECC. The CNIO Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, supported by grant PT13/0001. N.I. and J.M. are funded by SAF2013-45504-R (MINECO). J.M. is also supported by Ramon y Cajal Programme (MINECO) RYC-2012-10651. M.C.-A. and X.C. were funded by the Immutrain Marie Skodowska-Curie ITN Grant. S.H. received funding from the European Union's Horizon 2020 Research and Innovation Programme under grant agreement numberS

Recommendations regarding the diagnostic tests.

<p>Recommendations regarding the diagnostic tests.</p

Recommendations regarding the clinical phenotypes and multidimensional evaluation.

<p>Recommendations regarding the clinical phenotypes and multidimensional evaluation.</p

Clinical characteristics of the audited cases (n = 621).

<p>Clinical characteristics of the audited cases (n = 621).</p