RISalud-ANDALUCÍA
Not a member yet
18682 research outputs found
Sort by
CroniCare: Platform for the Design and Implementation of Follow-Up, Control and Self-Management Interventions for Chronic and Multimorbidity Patients Based on Mobile Technologies.
No full textThe project proposes to facilitate the design and evaluation of interventions based on mobile technologies and information systems in order to improve the capacity for self-management, empowerment and control of chronic and multimorbidity patients. The system allows to create customizable apps according to the needs of primary care and specialized care. The project includes an evaluation of the impact of the care model, as well as the effectiveness and efficiency of the intervention through a study with 124 multimorbidity patients
Evaluation of poly (lactic-co-glycolic acid) nanoparticles to improve the therapeutic efficacy of paclitaxel in breast cancer
No full textIntroduction: Paclitaxel (PTX) is a cornerstone in the treatment of breast cancer, the most common type of cancer in women. However, this drug has serious limitations, including lack of tissue-specificity, poor water solubility, and the development of drug resistance. The transport of PTX in a polymeric nanoformulation could overcome these limitations.Methods: In this study, PLGA-PTX nanoparticles (NPs) were assayed in breast cancer cell lines, breast cancer stem cells (CSCs) and multicellular tumor spheroids (MTSs) analyzing cell cycle, cell uptake (Nile Red-NR-) and alpha-tubulin expression. In addition, PLGA-PTX NPs were tested in vivo using C57BL/6 mice, including a biodistribution assay.Results: PTX-PLGA NPs induced a significant decrease in the PTX IC50 of cancer cell lines (1.31 and 3.03-fold reduction in MDA-MB-231 and E0771 cells, respectively) and CSCs. In addition, MISs treated with PTX-PLGA exhibited a more disorganized surface and significantly higher cell death rates compared to free PTX (27.9% and 16.3% less in MRCSs from MCF-7 and E0771, respectively). PTX-PLGA nanoformulation preserved PTX's mechanism of action and increased its cell internalization. Interestingly, PTX-PLG A NI's not only reduced the tumor volume of treated mice hut also increased the antineoplastic drug accumulation in their lungs, liver, and spleen. In addition, mice treated with PTX-loaded NPs showed blood parameters similar to the control mice, in contrast with free PTX.Conclusion: These results suggest that our PTX-PLGA NPs could be a suitable strategy for breast cancer therapy, improving antitumor drug efficiency and reducing systemic toxicity without altering its mechanism of action.Financial support from the V Plan Propio (University of Seville). This
work was also supported by Consejería de Salud de la Junta de Andalucía
(PI-0102-2017 and P18-HO-3882) and Instituto de Salud Carlos III
(ISCIII) (Project PI19/01478) (FEDER).S
Expert Panel Guidance and Narrative Review of Treatment Simplification of Complex Insulin Regimens to Improve Outcomes in Type 2 Diabetes.
No full textGiven the progressive nature of type 2 diabetes (T2D), most individuals with the disease will ultimately undergo treatment intensification. This usually involves the stepwise addition of a new glucose-lowering agent or switching to a more complex insulin regimen. However, complex treatment regimens can result in an increased risk of hypoglycaemia and high treatment burden, which may impact negatively on both therapeutic adherence and overall quality of life. Individuals with good glycaemic control may also be overtreated with unnecessarily complex regimens. Treatment simplification aims to reduce individual treatment burden, without compromising therapeutic effectiveness or safety. Despite data showing that simplifying therapy can achieve good glycaemic control without negatively impacting on treatment efficacy or safety, it is not always implemented in clinical practice. Current clinical guidelines focus on treatment intensification, rather than simplification. Where simplification is recommended, clear guidance is lacking and mostly focused on treatment of the elderly. An expert, multidisciplinary panel evaluated the current treatment landscape with respect to guidance, published evidence, recommendations and approaches regarding simplification of complex insulin regimens. This article outlines the benefits of treatment simplification and provides practical recommendations on simplifying complex insulin treatment strategies in people with T2D using illustrative cases.S
Clinical improvements after treatment with a low-valine and low-fat diet in a pediatric patient with enoyl-CoA hydratase, short chain 1 (ECHS1) deficiency.
No full textEnoyl-CoA hydratase short-chain 1 (ECHS1) is a key mitochondrial enzyme that is involved in valine catabolism and fatty acid beta-oxidation. Mutations in the ECHS1 gene lead to enzymatic deficiency, resulting in the accumulation of certain intermediates from the valine catabolism pathway. This disrupts the pyruvate dehydrogenase complex and the mitochondrial respiratory chain, with consequent cellular damage. Patients present with a variable age of onset and a wide spectrum of clinical features. The Leigh syndrome phenotype is the most frequently reported form of the disease. Herein, we report a case of a male with ECHS1 deficiency who was diagnosed at 8 years of age. He presented severe dystonia, hyperlordosis, moderate to severe kyphoscoliosis, great difficulty in walking, and severe dysarthria. A valine-restricted and total fat-restricted diet was considered as a therapeutic option after the genetic diagnosis. An available formula that restricted branched-chain amino acids and especially restricted valine was used. We also restricted animal protein intake and provided a low-fat diet that was particularly low in dairy fat. This protein- and fat-restricted diet was initiated with adequate tolerance and adherence. After three years, the patient noticed an improvement in dystonia, especially in walking. He currently requires minimal support to walk or stand. Therefore, he has enhanced his autonomy to go to school or establish a career for himself. His quality of life and motivation for treatment have greatly increased. There is still a substantial lack of knowledge about this rare disorder, especially knowledge about future effective treatments. However, early diagnosis and treatment with a valine- and fat-restricted diet, particularly dairy fat-restricted diet, appeared to limit disease progression in this patient with ECHS1 deficiency.S
Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice.
No full textMetabolic associated fatty liver disease (MAFLD) is a hepatic manifestation of metabolic syndrome and usually associated with obesity and diabetes. Our aim is to characterize the pathophysiological mechanism involved in MAFLD development in Black Tan and brachyuric (BTBR) insulin-resistant mice in combination with leptin deficiency (ob/ob). We studied liver morphology and biochemistry on our diabetic and obese mice model (BTBR ob/ob) as well as a diabetic non-obese control (BTBR + streptozotocin) and non-diabetic control mice (BTBR wild type) from 4-22 weeks. Lipid composition was assessed, and lipid related pathways were studied at transcriptional and protein level. Microvesicular steatosis was evident in BTBR ob/ob from week 6, progressing to macrovesicular in the following weeks. At 12th week, inflammatory clusters, activation of STAT3 and Nrf2 signaling pathways, and hepatocellular ballooning. At 22 weeks, the histopathological features previously observed were maintained and no signs of fibrosis were detected. Lipidomic analysis showed profiles associated with de novo lipogenesis (DNL). BTBR ob/ob mice develop MAFLD profile that resemble pathological features observed in humans, with overactivation of inflammatory response, oxidative stress and DNL signaling pathways. Therefore, BTBR ob/ob mouse is an excellent model for the study of the steatosis to steatohepatitis transition.S
Immunotherapy in Advanced Prostate Cancer: Current Knowledge and Future Directions.
No full textThe advent of immunotherapy has revolutionized cancer treatment. Unfortunately, this has not been the case for metastatic castration-resistant prostate cancer (mCRPC), likely due to the heterogeneous and immune-suppressive microenvironment present in prostate cancer. The identification of molecular biomarkers that could predict response to immunotherapy represents one of the current challenges in this clinical scenario. The management of advanced castration-resistant prostate cancer is rapidly evolving and immunotherapy treatments, mostly consisting of immune checkpoint inhibitors combinations, BiTE® (bispecific T-cell engager) immune therapies, and chimeric antigen receptors (CAR) are in development with promising results. This review analyses the current evidence of immunotherapy treatments for mCRPC, evaluating past failures and promising approaches and discussing the directions for future research
How Meaningful Are Minor Details in the Generation of Nanomodified Electrochemical Enzyme Biosensors? Exploring the Scenario with Sinusoidal Approaches
No full textIn this work, a screening of Sonogel-Carbon (SNGC) electrodes modified with nanomaterials (carbon nanotubes and gold nanoparticles) and the study of their effect on the electrochemical performance of sinusoidal voltage (SV) and current (SC)-based biosensors are reported. Surface modification was achieved by drop-casting and electrodeposition methodologies. Within the strategies used, SV and SC, recently exploited procedures, were used to electrodeposit simultaneously a poly 3,4-ethylenedioxythiophene (PEDOT)-tyrosinase layer and the corresponding nanostructured material. Dopamine was selected as a benchmark analyte to evaluate the analytical performance of the different (bio)sensors obtained in terms of relevant figures of merit, such as sensitivity, limits of detection and quantitation, and accuracy, among others. A discussion about the pros and cons between the type of modification and the methods employed is also presented. Briefly, SC based sensors offered excellent quality analytical parameters and lower dispersion of the results. They were employed for more specific electrochemical studies, including interferences assays and the determination of DA in real samples, obtaining good recoveries (101-110.6%). The biosensor modified with gold nanoparticles (AuNPs) (drop-casting method) and SC-electrodeposited showed the best figures of merit: R-2 = 0.999; sensitivity = -4.92 x 10(-9) A.mu M-1; RSDsensitivity = 1.60%; LOD = 5.56 mu M; RSDLOD = 6.10%; and LOQ = 18.53 mu M.Authors thank Electron Microscopy Division from Servicios Centrales de Investigación Científica y Tecnológica of University of Cadiz (SC-ICYT UCA) for their technical assistance during SEM measurements.S
Decomposition: Partition as an Escape from Decay - A Gestalt of the Obsessive Life-World.
No full textAccording to phenomenological literature, the life-world of the obsessive subject is characterized by its claustrophobic closure, the attempt to stop the flow of time, and the inability to accept the formlessness hidden behind the form. The obsessive obstinately tries to build defences against what he cannot tolerate of reality and this effort causes loss of spontaneity in the pre-reflective dimension of existence, resulting in the thought process being oversaturated and ending up by blocking action. Our proposal is to unpack the phenomenon of partition in the obsessive's world, analysing the similarities and differences with the schizophrenic life-world. In fact, although the mechanization and the predominance of a reflective dimension are similar in these psychopathological typologies, these phenomena are based on completely different foundations: the ontological question in the case of the schizophrenic subject, while the ontic question in the case of the obsessive subject. By decomposing reality, the obsessive tries to stem the dimension of the formless, which is hidden under the representative order of things which he cannot tolerate. Understanding the hyper-rationalizing tendency of obsessive thought offers important clinical implications by providing shareable insights into psychotherapeutic development
A Noninvasive Method for Time-Lapse Imaging of Microbial Interactions and Colony Dynamics.
No full textComplex interactions between microbial populations can greatly affect the overall properties of a microbial community, sometimes leading to cooperation and mutually beneficial coexistence, or competition and the death or displacement of organisms or subpopulations. Interactions between different biofilm populations are highly relevant in diverse scientific areas, from antimicrobial resistance to microbial ecology. The utilization of modern microscopic techniques has provided a new and interesting insight into how bacteria interact at the cellular level to form and maintain microbial biofilms. However, our ability to follow complex intraspecies and interspecies interactions in vivo at the microscopic level has remained somewhat limited. Here, we detailed BacLive, a novel noninvasive method for tracking bacterial growth and biofilm dynamics using high-resolution fluorescence microscopy and an associated ImageJ processing macro (https://github.com/BacLive) for easier data handling and image analysis. Finally, we provided examples of how BacLive can be used in the analysis of complex bacterial communities. IMPORTANCE Communication and interactions between single cells are continuously defining the structure and composition of microbial communities temporally and spatially. Methods routinely used to study these communities at the cellular level rely on sample manipulation which makes microscopic time-lapse experiments impossible. BacLive was conceived as a method for the noninvasive study of the formation and development of bacterial communities, such as biofilms, and the formation dynamics of specialized subpopulations in time-lapse experiments at a colony level. In addition, we developed a tool to simplify the processing and analysis of the data generated by this method.S
Community-acquired bacteraemia by Klebsiella pneumoniae producing KPC-3 and resistant to ceftazidime/avibactam.
No full textTo describe the clinical and microbiological features of a case of community-acquired infection by KPC-producing K. pneumoniae (KPCKP) resistant to ceftazidime/avibactam (CAZ-AVI). Identification of microorganisms was performed with MALDI Biotyper CA System (BrukerDaltonics, Madrid, Spain). Antimicrobial susceptibility testing was performed using Sensitre EURGNCOL panels (Thermo Fisher Scientific, Madrid, Spain) and gradient strips (Etest, bioMérieux, Madrid, Spain) in the case of CAZ-AVI, using EUCAST breakpoints for interpretation. Whole genome sequencing of blood culture and rectal swab isolates was performed using the Illumina NovaSeq 6000 sequencing system, with 2 × 150-bp paired-end reads (Illumina, Inc.). Blood culture and rectal swab KPCKP isolates were resistant to carbapenems and to CAZ-AVI. The blood culture isolate showed susceptibility to trimethoprim-sulfamethoxazole (TMP-SMX), but the rectal swab culture isolate was resistant to this antibiotic. Both isolates belonged to clonal lineage ST512, harboured a single copy of blaKPC-3 gene, and showed 16 single nucleotide polymorphisms (SNP) between them and 38 SNPs with regard to the first KPC-3 producing K. pneumoniae isolated in our hospital in an initial outbreak in 2012. Genome-wide resistome analysis revealed the presence of a IncFIB(K) plasmid harbouring sul1 and dfrA12 genes only in the rectal swab culture isolate, which may explain its resistance to TMP-SMX. Resistance to ceftazidime-avibactam is an emerging nosocomial problem. This case shows that CAZ-AVI-resistant KPCKP strains may disseminate into the community and cause serious infections.S