Importance of specialized paediatric and neonatal transport. Current situation in Spain: Towards a more equitable and universal future

Transporte neonatal; Transporte interhospitalario; Cuidados críticosNeonatal transport; Interfacility transport; Critical careTransport neonatal; Transport interhospitalari; Cures crítiquesEl transporte pediátrico y neonatal especializado es un recurso útil y esencial en el traslado interhospitalario de estos pacientes. Permite acercar los recursos materiales y personales de una unidad de cuidados intensivos a los hospitales comarcales donde se pueda encontrar el paciente. Los beneficios de estos equipos están muy bien demostrados en la literatura. Estas unidades deberían formar parte de los sistemas de emergencias, al mismo tiempo que sería recomendable que estuvieran constituidas por personal integrado en los hospitales terciarios con el fin de mantener las habilidades y competencias necesarias. El equipo, compuesto por médicos, enfermeros y técnicos de emergencias sanitarias, tiene que dominar tanto la fisiopatología del transporte como la del paciente crítico en este rango de edad. Es importante una alta calidad tanto humana como asistencial, por lo que la formación continuada y el reciclaje periódico serán imprescindibles para poder cumplir correctamente con los indicadores de calidad en transporte. Así mismo, es fundamental contar con vehículos propios y adaptados a su función, que permitan llevar la gran variedad de material necesario, así como la electromedicina que se requiere. Sin embargo, en España este modelo de transporte pediátrico y neonatal no está estandarizado y por lo tanto no es homogéneo: existen diferentes modelos que no siempre aportan una adecuada calidad, siendo necesaria la implantación de unidades especializadas en todo el país para garantizar un transporte sanitario de calidad a cualquier niño o neonato crítico.Specialized paediatric and neonatal transport is a useful and essential resource in the interhospital transfer of these patients. It allows bringing the material and personal resources of an intensive care unit closer to the regional hospitals where the patient can be found. The benefits of these teams are very well demonstrated in the literature. These units should be part of the emergency systems, while it would be recommended that they would be staff integrated in the tertiary hospitals, in order to maintain the necessary skills and competencies. The team, made up of physicians, nurses and emergency medical technicians, must master both the pathophysiology of transport and that of the critical patient in this age range. A high-quality of both human and care is important, so continuous training and periodic recycling will be essential to be compliant with the quality indicators in transport. Likewise, it is essential to have specific vehicles adapted to this function, which allow carrying the wide variety of necessary material, as well as the electromedicine that is required. However, in Spain this paediatric and neonatal transport model is not standardized and, therefore, is not homogeneous: there are different models that do not always provide adequate quality, making it necessary to implement specialized units throughout the country to guarantee sanitary transport quality to any critical child or neonate

Influence of Al distribution and defects concentration of ferrierite catalysts synthesized from Na-free gels in the skeletal isomerization of n-butene

The skeletal isomerization of n-butenes to isobutene has been carried out over ferrierite catalysts (Si/Al ~ 15) containing different acid sites distribution and different amount of defects. The zeolite crystals were synthesized under hydrothermal conditions in fluoride medium in the absence of alkaline cations by using suitable combinations of structure directing agents. Template-driven low density of acid sites in 10-membered-ring channels enhances the isobutene selectivity and decreases catalyst deactivation. The presence of high amount of silanol groups and Lewis acid sites increases the yields of by-products and catalysts decay.MICINN (CTQ2006-06282) CSIC (JAE-doc contract)Peer reviewe

Tailoring the acid strength of microporous silicoaluminophosphates through the use of mixtures of templates: Control of the silicon incorporation mechanism

SAPO-5 samples have been synthesized with triethylamine (TEA), benzylpyrrolidine (BP) and mixtures of them as structure directing agents (SDAs). It has been observed that in the as-synthesised materials the concentration of SDAs (molecules per unit cell) and the Si content are similar. According to the different molecular size of both SDAs, the samples exhibit higher organic weight and lower water content as the molar fraction of BP in the synthesis gel increases. These differences in selectivity for organic/water incorporation influences the mechanism of Si substitution in the AlPO lattice: the higher organic content obtained at higher BP/TEA ratio leads to the formation of large Si islands, while the higher water content of the sample obtained with TEA enhances the formation of isolated Si(OAl)4 environments. Interestingly, it has been found that these two opposite trends can be tailored to a certain point by using mixtures of both SDAs, TEA and BP, in the required ratio. The catalytic activity of the samples has been tested in the isomerisation of m-xylene. It has been observed a higher activity of samples obtained with BP as the main SDA, thus evidencing the better performance of large Si islands in this reaction.MEC (CTQ2006-06282)Peer reviewe

Relationships between Physical Activity Level and Pain in the Spanish Population: A Cross-Sectional Study

One third of the world’s population suffers from some form of pain. Physical inactivity is one of the causes that reduces physical fitness and may lead to an increase in the prevalence of pain in the population. Aims. To analyse the relationships between the level of physical activity (PAL) and the prevalence and degree of pain, the limitations and impact of pain on daily activities and the use of pain medication in the Spanish population. Hypothesis. PAL is related to pain among Spaniards. Methodology. A cross-sectional study design was used, based on data obtained from the Spanish National Health Survey 2017 with 17,777 participants. A descriptive analysis was performed. Nonparametric statistical tests were used: chi-square statistic to analyse intergroup differences in ordinal variables; Mann−Whitney U test to analyse intergroup differences in continuous variables. A correlation study was also performed between the variables of interest, using Spearman’s rho. Results. Relationships were found between PAL and: prevalence of pain, degree of pain, limitations due to pain in usual activities, level of impact in daily activities and use of pain medication in the Spanish population (p < 0.001). Performing moderate and intense PA was related to lower prevalence and degree of pain in the population that performed it, compared to those who only walked or were inactive. Weak correlations were found between the level of PA and the study variables (p < 0.001). Conclusions. High PALs in the population are related to better indicators of pain among Spaniards, appearing to reduce the prevalence and degree of pain, as well as the limitations and impact caused by pain in the daily activities of citizens, and could reduce the use of pain medication in the adult Spanish population.This research was funded by “Ayudas para la Realización de Actividades de Investigación y Desarrollo Tecnológico, de Divulgación y de Transferencia de Conocimiento por los Grupos de Investigación de Extremadura 2021”; Financed by the Junta de Extremadura and the European Social Fund. Grant number 2021/00461/001

Cancer-associated fibroblasts modify lung cancer metabolism involving ROS and TGF-β signaling

Lung cancer is a major public health problem due to its high incidence and mortality rate. The altered metabolism in lung cancer is key for the diagnosis and has implications on both, the prognosis and the response to treatments. Although Cancer-associated fibroblasts (CAFs) are one of the major components of the tumor microenvironment, little is known about their role in lung cancer metabolism. We studied tumor biopsies from a cohort of 12 stage IIIA lung adenocarcinoma patients and saw a positive correlation between the grade of fibrosis and the glycolysis phenotype (Low PGC-1α and High GAPDH/MT-CO1 ratio mRNA levels). These results were confirmed and extended to other metabolism-related genes through the in silico data analysis from 73 stage IIIA lung adenocarcinoma patients available in TCGA. Interestingly, these relationships are not observed with the CAFs marker α-SMA in both cohorts. To characterize the mechanism, in vitro co-culture studies were carried out using two NSCLC cell lines (A549 and H1299 cells) and two different fibroblast cell lines. Our results confirm that a metabolic reprogramming involving ROS and TGF-β signaling occurs in lung cancer cells and fibroblasts independently of α-SMA induction. Under co-culture conditions, Cancer-Associated fibroblasts increase their glycolytic ability. On the other hand, tumor cells increase their mitochondrial function. Moreover, the differential capability among tumor cells to induce this metabolic shift and also the role of the basal fibroblasts Oxphos Phosphorylation (OXPHOS) function modifying this phenomenon could have implications on both, the diagnosis and prognosis of patients. Further knowledge in the mechanism involved may allow the development of new therapies.Work in the authors’ laboratories is supported by ‘‘Instituto de Salud Carlos III’’ PI13/01806 and PIE14/0064 to M.P. A.C-B, received a Spanish Lung Cancer Group fellowship. R.L-B, is supported by Comunidad Autónoma de Madrid “Garantía juvenil” contract

Standard Non-Personalized Electric Field Modeling of Twenty Typical tDCS Electrode Configurations via the Computational Finite Element Method: Contributions and Limitations of Two Different Approaches

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation procedure to modulate cortical excitability and related brain functions. tDCS can effectively alter multiple brain functions in healthy humans and is suggested as a therapeutic tool in several neurological and psychiatric diseases. However, variability of results is an important limitation of this method. This variability may be due to multiple factors, including age, head and brain anatomy (including skull, skin, CSF and meninges), cognitive reserve and baseline performance level, specific task demands, as well as comorbidities in clinical settings. Different electrode montages are a further source of variability between tDCS studies. A procedure to estimate the electric field generated by specific tDCS electrode configurations, which can be helpful to adapt stimulation protocols, is the computational finite element method. This approach is useful to provide a priori modeling of the current spread and electric field intensity that will be generated according to the implemented electrode montage. Here, we present standard, non-personalized model-based electric field simulations for motor, dorsolateral prefrontal, and posterior parietal cortex stimulation according to twenty typical tDCS electrode configurations using two different current flow modeling software packages. The resulting simulated maximum intensity of the electric field, focality, and current spread were similar, but not identical, between models. The advantages and limitations of both mathematical simulations of the electric field are presented and discussed systematically, including aspects that, at present, prevent more widespread application of respective simulation approaches in the field of non-invasive brain stimulatio

BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging

血液脳関門開放術による遺伝子治療法の開発 --身体を傷つけない脳疾患の治療を目指して--. 京都大学プレスリリース. 2023-04-20.Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson’s disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson’s disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition

Background: Platinum-based chemotherapy remains the standard of care for most lung cancer cases. However chemoresistance is often developed during the treatment, limiting clinical utility of this drug. Recently, the ability of tumor cells to adapt their metabolism has been associated to resistance to therapies. In this study, we first described the metabolic reprogramming of Non-Small Cell Lung Cancer (NSCLC) in response to cisplatin treatment. Methods: Cisplatin-resistant versions of the A549, H1299, and H460 cell lines were generated by continuous drug exposure. The long-term metabolic changes, as well as, the early response to cisplatin treatment were analyzed in both, parental and cisplatin-resistant cell lines. In addition, four Patient-derived xenograft models treated with cisplatin along with paired pre- and post-treatment biopsies from patients were studied. Furthermore, metabolic targeting of these changes in cell lines was performed downregulating PGC-1α expression through siRNA or using OXPHOS inhibitors (metformin and rotenone). Results: Two out of three cisplatin-resistant cell lines showed a stable increase in mitochondrial function, PGC1-α and mitochondrial mass with reduced glycolisis, that did not affect the cell cycle. This phenomenon was confirmed in vivo. Post-treatment NSCLC tumors showed an increase in mitochondrial mass, PGC-1α and a decrease in the GAPDH/MT-CO1 ratio. In addition, we demonstrated how a ROS-mediated metabolism reprogramming, involving PGC-1α and increased mitochondrial mass, is induced during short-time cisplatin exposure. Moreover, we tested how cells with increased PGC-1a induced by ZLN005 treatment, showed reduced cisplatin-driven apoptosis. Remarkably, the long-term metabolic changes, as well as the metabolic reprogramming during short-time cisplatin exposure can be exploited as an Achilles’ heel of NSCLC cells, as demonstrated by the increased sensitivity to PGC-1α interference or OXPHOS inhibition using metformin or rotenone. Conclusion: These results describe a new cisplatin resistance mechanism in NSCLC based on a metabolic reprogramming that is therapeutically exploitable through PGC-1α downregulation or OXPHOS inhibitors.Work in the authors’ laboratories is supported by ‘‘Instituto de Salud Carlos III’’ PI13/01806 and PIE14/0064 to M.P. A.C-B, received a Spanish Lung Cancer Group fellowship. R.L-B, is supported by Comunidad Autónoma de Madrid “Garantía juvenil” contrac

Differences in peripheral and tissue immune cell populations following haematopoietic stem cell transplantation in Crohn's disease patients

Background and aims: recent studies have shown the efficacy of autologous haematopoietic stem cell transplantation [HSCT] in severely refractory Crohn's disease [CD] patients. HSCT is thought to eliminate auto-reactive cells; however, no specific studies of immune reconstitution in CD patients are available. Methods: we followed a group of CD patients [n = 18] receiving autologous HSCT, with 50% of them achieving endoscopic drug-free remission. To elucidate the mechanisms driving efficacy, we monitored changes after HSCT in blood and intestine immune-cell composition. CD patients [n = 22] receiving anti-tumour necrosis factor [TNF]-α were included for comparison. Results: severe immune ablation followed by HSCT induced dramatic changes in both peripheral blood T and B cells in all patients regardless of the efficacy of the treatment. Endoscopic remission at week 52 following HSCT was associated with significant intestinal transcriptional changes. A comparison of the remission signature with that of anti-TNFα identified both common and unique genes in the HSCT-induced response. Based on deconvolution analysis of intestinal biopsy transcriptome data, we show that response to HSCT, but not to anti-TNFα, is associated with an expansion of naïve B-cells, as seen in blood, and a decrease in the memory resting T-cell content. As expected, endoscopic remission, in response to both HSCT and anti-TNFα, led to a significant reduction in intestinal neutrophil and M1 macrophage content. Conclusions: peripheral blood immune remodelling after HSCT does not predict efficacy. In contrast, a profound intestinal T-cell depletion that is maintained long after transplant is associated with mucosal healing following HSCT, but not anti-TNFα

Gastrointestinal cancer: Relationship between histology and microbiota

Este trabajo fue presentado como comunicación tipo póster en el citado congreso.Objectives: Review of the published literature concerning the relationship between microbiome and gastrointestinal cancer. Methods: Present work is focused on systematic research in the most prominent biomedical databases finds relevant works in Pubmed and the library’s catalog of the University of Málaga (Jábega) of published journals in the last 5 years. Results: In this work, the mechanisms used by the microbiome to damage gastrointestinal epithelial cells and cause cancer are explained. Some of them are the dysbiosis, destruction of the mucosal barrier, chronic inflammation, damage caused by metabolites produced in the digestion and the direct attack of certain toxins to the cell’s DNA. These mechanisms adjust the immune response, by activation or inhibition using different cytokines. There is also a deeper look into several microorganisms and how they cause gastrointestinal cancer using toxins or virulence factors to activate them. Conclusions: The evidence found so far about the microbiota and gastrointestinal cancer is enough to assume the relationship between them, although there is much left to research. With these findings, it can be expected that in a near future certain microorganisms could be used for screening purposes, due to their increase in early stages of the tumor genesis and also, in a preventive way to try to eradicate them, even avoid cancer. Studies on the microbiota are hardly beginning, and results appear to be promising.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech