Delphi sobre la política sanitaria española en el siglo XXI

El presente trabajo recoge parte de una investigación sociológica sobre los problemas fundamentales del sector sanitario español utilizando un Delphi. Se realiza durante la década de los noventa a una conjunto de los mejores expertos españoles (varones y mujeres) sobre salud y sanidad. La investigación supone la definición de quince problemas específicos sobre la descentralización y reforma del sistema sanitario español. Todas las personas de la muestra contestan a las quince preguntas base, y las entrevistas son luego transcritas. A continuación aparece un análisis sobre las diversas actitudes, razonamientos, y opiniones sobre la política sanitaria en España de cara al siglo XXI. Se presenta una agenda de problemas para resolver desde la política sanitaria tanto pública como privada. Es un documento indispensable para analizar las políticas públicas respecto del sector sanitario español

Respiratory syncytial virus hospitalization in children in northern Spain

Objectives: Understanding respiratory syncytial virus (RSV) morbidity may help to plan health care and future vaccine recommendations. We aim to describe the characteristics and temporal distribution of children diagnosed with RSV admitted in a Spanish hospital. Methods: Descriptive study for which the hospital discharges of children < 5 years of age with RSV infection were analyzed. The information was extracted from the hospital discharge database of a reference pediatric hospital in northern Spain for the 2010-2011 to 2014-2015 RSV seasons. Results: Six hundred and forty-seven hospitalizations of children with RSV infection were analyzed, 94% of which occurred between the second week of November and the last week of March. Most children (72%) were under one year of age and 95% were previously healthy infants. Infants born from October to December had the highest risk of hospitalization in the first year of life. The median length of hospital stay of children with and without comorbidities was six and three days, respectively. 6.5% of the hospitalized cases were admitted to the pediatric intensive care unit; this percentage was higher among children < 2 months (adjusted odds ratio 4.15; 95% confidence interval: 1.37-12.61) or with comorbidities (adjusted odds ratio 4.15; 95% confidence interval: 1.53-11.28). The case lethality was 0.3%. Conclusions: The risk of hospitalizations for RSV is high during the first year of life and increases among infants born in the fall. Being under two months of age and presenting comorbidities are the main risk factors associated to pediatric intensive care unit admission

Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients

Altered liver gene expression in CCl4-cirrhotic rats is partially normalized by insulin-like growth factor-I

We have previously shown that the administration of low doses of insulin-like growth factor-I (IGF-I) to CCl4-cirrhotic rats improves liver function and reduces fibrosis. To better understand the mechanisms behind the hepatoprotective effects of IGF-I, and to identify those genes whose expression is affected in cirrhosis and after IGF-1 treatment, we have performed differential display of mRNA analysis by means of polymerase chain reaction (PCR) in livers from control and CCl4-cirrhotic rats treated or not with IGF-I. We have identified 16 genes that were up- or down-regulated in the cirrhotic liver. IGF-I treatment partially normalized the expression of eight of these genes, including serine proteinase inhibitors such as serpin-2 and alpha-1-antichymotripsin, alpha-1-acid glycoprotein, and alpha-2u-globulin. Additionally, we show that IGF-I enhanced the regenerative activity in the cirrhotic liver, as determined by the increased expression of the proliferating cell nuclear antigen (PCNA). Finally, IGF-I treatment partially restored the expression of growth hormone receptor (GHR) and the levels of global genomic DNA methylation, which are reduced in human and experimental cirrhosis. Taken together, our observations confirm the hepatoprotective effects of IGF-I, and suggest that this action can be exerted in part through the normalization of liver gene expression, growth hormone (GH) responsiveness and global genomic DNA methylation

Changes in brown adipose tissue lipid mediator signatures with aging, obesity, and DHA supplementation in female mice

Brown adipose tissue (BAT) dysfunction in aging and obesity has been related to chronic unresolved inflammation, which could be mediated by an impaired production of specialized proresolving lipid mediators (SPMs), such as Lipoxins-LXs, Resolvins-Rvs, Protectins-PDs, and Maresins-MaRs. Our aim was to characterize the changes in BAT SPMs signatures and their association with BAT dysfunction during aging, especially under obesogenic conditions, and their modulation by a docosahexaenoic acid (DHA)-rich diet. Lipidomic, functional, and molecular studies were performed in BAT of 2-and 18-month- old lean (CT) female mice and in 18-month- old diet-induced obese (DIO) mice fed with a high-fat diet (HFD), or a DHA-enriched HFD. Aging downregulated Prdm16 and UCP1 levels, especially in DIO mice, while DHA partially restored them. Arachidonic acid (AA)-derived LXs and DHA-derived MaRs and PDs were the most abundant SPMs in BAT of young CT mice.Interestingly, the sum of LXs and of PDs were significantly lower in aged DIO mice compared to young CT mice. Some of the SPMs most significantly reduced in obese-aged mice included LXB4, MaR2, 4S,14S-diHDHA, 10S,17S-diHDHA (a.k.a. PDX), and RvD6. In contrast, DHA increased DHA-derived SPMs, without modifying LXs. However, MicroPET studies showed that DHA was not able to counteract the impaired cold exposure response in BAT of obese-aged mice. Our data suggest that a defective SPMs production could underlie the decrease of BAT activity observed in obese-aged mice, and highlight the relevance to further characterize the physiological role and therapeutic potential of specific SPMs on BAT development and function

Efecto de una cepa de Fusarium oxysporum y de diversas levaduras sobre la nutrición férrica de plantas de pepino y tomate

Trabajo presentado en el XVI Congreso Nacional de Ciencias Hortícolas, celebrado en Córdoba del 17 al 22 de octubre de 2021,El hierro (Fe) es un micronutriente esencial para las plantas. En suelos calizos se encuentra en su forma oxidada (Fe 3+), presentando baja solubilidad y disponibilidad para las plantas. Bajo deficiencia de Fe, las plantas dicotiledóneas inducen diversas respuestas fisiológicas y morfológicas en sus raíces para facilitar así su captación y paliar los efectos que produce su deficiencia. Existen evidencias de que determinados microorganismos rizosféricos, como los que provocan la Respuesta Sistémica Inducida (ISR), pueden facilitar la nutrición férrica de las plantas. El objetivo de este trabajo ha sido, por una parte, estudiar el efecto de la cepa no patogénica de Fusarium oxysporum (FO12), posiblemente inductora de ISR, sobre el crecimiento y clorosis de plantas de tomate (Solanum lycopersicum Mill.), y sobre la colonización de raíces de pepino (Cucumis sativus L.). Por otra parte, estudiar el efecto de determinadas levaduras (Debaryomyces hansenii, Saccharomyces cerevisiae y Hansenula polymorpha) sobre diversas respuestas a la deficiencia de Fe en plantas de pepino. Los experimentos con tomate se han desarrollado en suelo calizo y los de pepino en cultivo hidropónico. Los resultados obtenidos con FO12 han mostrado su capacidad para colonizar endofiticamente las raíces de pepino y su efecto promotor del crecimiento, la concentración de clorofila y de Fe (en hojas) en plantas de tomate. Las diferentes levaduras utilizadas han causado inducción de la capacidad reductora de Fe 3+, de la acidificación de la rizosfera, y de la proliferación de pelos radicales en la zona subapical de las raíces de pepino. Estos resultados sugieren que, tanto FO12 como las diferentes levaduras utilizadas, tienen potencial como biofertilizantes de Fe.Plan Propio de la Universidad de Córdoba y Ministerio de Ciencia e Innovación

A synthetic peptide from transforming growth factor beta type III receptor inhibits liver fibrogenesis in rats with carbon tetrachloride liver injury

Transforming growth factor beta1 (TGF-beta1) is a pleiotropic cytokine, which displays potent profibrogenic effects and is highly expressed in fibrotic livers. For this reason, development of TGF-B1 inhibitors might be of great importance to control liver fibrogenesis as well as other undesired side effects due to this cytokine. Potential peptide inhibitors of TGF-beta1 (derived from TGF-beta1 and from its type III receptor) were tested in vitro and in vivo using different assays. Peptides P11 and P12, derived from TGF-beta1, and P54 and P144, derived from its type III receptor, prevented TGF-beta1-dependent inhibition of MV1Lu proliferation in vitro and markedly reduced binding of TGF-beta1 to its receptors. P144 blocked TGF-beta1-dependent stimulation of a reporter gene under the control of human alpha2(I) collagen promoter. Intraperitoneal administration of P144 also showed potent antifibrogenic activity in vivo in the liver of rats receiving CCl4. These rats also showed a significant decrease in the number of activated hepatic stellate cells as compared with those treated with saline only. These results suggest that short synthetic peptides derived from TGF-beta1 type III receptor may be of value in reducing liver fibrosis in chronic liver injury

Circulating free insulin-like growth factor-I and prostate cancer: a case-control study nested in the European prospective investigation into cancer and nutrition

Background: Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. Methods: We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. Results: Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. Conclusions: Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk

GABAergic deficits in absence of LPA1 receptor, associated anxiety-like and coping behaviors, and amelioration by interneuron precursor transplants into the dorsal hippocampus

Defects in GABAergic function can cause anxiety- and depression-like behaviors among other neuropsychiatric disorders. Therapeutic strategies using the transplantation of GABAergic interneuron progenitors derived from the medial ganglionic eminence (MGE) into the adult hippocampus reversed the symptomatology in multiple rodent models of interneuron-related pathologies. In turn, the lysophosphatidic acid receptor LPA has been reported to be essential for hippocampal function. Converging evidence suggests that deficits in LPA receptor signaling represent a core feature underlying comparable hippocampal dysfunction and behaviors manifested in common neuropsychiatric conditions. Here, we first analyzed the GABAergic interneurons in the hippocampus of wild-type and maLPA-null mice, lacking the LPA receptor. Our data revealed a reduction in the number of neurons expressing GABA, calcium-binding proteins, and neuropeptides such as somatostatin and neuropeptide Y in the hippocampus of maLPA-null mice. Then, we used interneuron precursor transplants to test links between hippocampal GABAergic interneuron deficit, cell-based therapy, and LPA receptor-dependent psychiatric disease-like phenotypes. For this purpose, we transplanted MGE-derived interneuron precursors into the adult hippocampus of maLPA-null mice, to test their effects on GABAergic deficit and behavioral symptoms associated with the absence of the LPA receptor. Transplant studies in maLPA-null mice showed that grafted cells were able to restore the hippocampal host environment, decrease the anxiety-like behaviors and neutralize passive coping, with no abnormal effects on motor activity. Furthermore, grafted MGE-derived cells maintained their normal differentiation program. These findings reinforce the use of cell-based strategies for brain disorders and suggest that the LPA receptor represents a potential target for interneuron-related neuropsychiatric disorders.This work was supported by grants from the Spanish Ministry of Science, Innovation and Universities, co-funded by the European Regional Development Fund (ERDF, EU), (PSI2017-82604R, to LJS; PSI2017-83408-P to CP; SAF09-07746, to MAD; PI16/01510, to GET) and Andalusian Regional Ministries of Economy, Knowledge, Business and University (SEJ-4515 -to LJS; SEJ1863 to CP) and of Health and Families (Nicolas Monardes Programme to GET)