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1.
Int J Mol Sci ; 25(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38891922

RESUMEN

Vascular calcification has a global health impact that is closely linked to bone loss. The Receptor Activator of Nuclear Factor Kappa B (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system, fundamental for bone metabolism, also plays an important role in vascular calcification. The Leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4), a novel receptor for RANKL, regulates bone remodeling, and it appears to be involved in vascular calcification. Besides RANKL, LGR4 interacts with R-spondins (RSPOs), which are known for their roles in bone but are less understood in vascular calcification. Studies were conducted in rats with chronic renal failure fed normal or high phosphorus diets for 18 weeks, with and without control of circulating parathormone (PTH) levels, resulting in different degrees of aortic calcification. Additionally, vascular smooth muscle cells (VSMCs) were cultured under non-calcifying (1 mM phosphate) and calcifying (3 mM phosphate) media with different concentrations of PTH. To explore the role of RANKL in VSMC calcification, increasing concentrations of soluble RANKL were added to non-calcifying and calcifying media. The effects mediated by RANKL binding to its receptor LGR4 were investigated by silencing the LGR4 receptor in VSMCs. Furthermore, the gene expression of the RANK/RANKL/OPG system and the ligands of LGR4 was assessed in human epigastric arteries obtained from kidney transplant recipients with calcification scores (Kauppila Index). Increased aortic calcium in rats coincided with elevated systolic blood pressure, upregulated Lgr4 and Rankl gene expression, downregulated Opg gene expression, and higher serum RANKL/OPG ratio without changes in Rspos gene expression. Elevated phosphate in vitro increased calcium content and expression of Rankl and Lgr4 while reducing Opg. Elevated PTH in the presence of high phosphate exacerbated the increase in calcium content. No changes in Rspos were observed under the conditions employed. The addition of soluble RANKL to VSMCs induced genotypic differentiation and calcification, partly prevented by LGR4 silencing. In the epigastric arteries of individuals presenting vascular calcification, the gene expression of RANKL was higher. While RSPOs show minimal impact on VSMC calcification, RANKL, interacting with LGR4, drives osteogenic differentiation in VSMCs, unveiling a novel mechanism beyond RANKL-RANK binding.


Asunto(s)
Músculo Liso Vascular , Ligando RANK , Receptores Acoplados a Proteínas G , Calcificación Vascular , Ligando RANK/metabolismo , Ligando RANK/genética , Animales , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Ratas , Humanos , Masculino , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Osteoprotegerina/metabolismo , Osteoprotegerina/genética , Hormona Paratiroidea/metabolismo , Células Cultivadas , Ratas Sprague-Dawley
2.
Sensors (Basel) ; 24(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38931502

RESUMEN

Robotic inspection is advancing in performance capabilities and is now being considered for industrial applications beyond laboratory experiments. As industries increasingly rely on complex machinery, pipelines, and structures, the need for precise and reliable inspection methods becomes paramount to ensure operational integrity and mitigate risks. AI-assisted autonomous mobile robots offer the potential to automate inspection processes, reduce human error, and provide real-time insights into asset conditions. A primary concern is the necessity to validate the performance of these systems under real-world conditions. While laboratory tests and simulations can provide valuable insights, the true efficacy of AI algorithms and robotic platforms can only be determined through rigorous field testing and validation. This paper aligns with this need by evaluating the performance of one-stage models for object detection in tasks that support and enhance the perception capabilities of autonomous mobile robots. The evaluation addresses both the execution of assigned tasks and the robot's own navigation. Our benchmark of classification models for robotic inspection considers three real-world transportation and logistics use cases, as well as several generations of the well-known YOLO architecture. The performance results from field tests using real robotic devices equipped with such object detection capabilities are promising, and expose the enormous potential and actionability of autonomous robotic systems for fully automated inspection and maintenance in open-world settings.

3.
Sensors (Basel) ; 24(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38793995

RESUMEN

A broadband differential-MMIC low-noise amplifier (DLNA) using metamorphic high-electron-mobility transistors of 70 nm in Gallium Arsenide (70 nm GaAs mHEMT technology) is presented. The design and results of the performance measurements of the DLNA in the frequency band from 1 to 16 GHz are shown, with a high dynamic range, and a noise figure (NF) below 1.3 dB is obtained. In this work, two low-noise amplifiers (LNAs) were designed and manufactured in the OMMIC foundry: a dual LNA, which we call balanced, and a differential LNA, which we call DLNA. However, the paper focuses primarily on DLNA because of its differential architecture. Both use a 70 nm GaAs mHEMT space-qualified technology with a cutoff frequency of 300 GHz. With a low power bias Vbias/Ibias (5 V/40.5 mA), NF < 1.07 dB "on wafer" was achieved, from 2 to 16 GHz; while with the measurements made "on jig", NF = 1.1 dB, from 1 to 10 GHz. Furthermore, it was obtained that NF < 1.5 dB, from 1 to 16 GHz, with a figure of merit equal to 145.5 GHz/mW. Finally, with the proposed topology, several LNAs were designed and manufactured, both in the OMMIC process and in other foundries with other processes, such as UMS. The experimental results showed that the NF of the DLNA MMIC with multioctave bandwidth that was built in the frequency range of the L-, S-, C-, and X-bands was satisfactory.

4.
Lancet HIV ; 11(6): e389-e405, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38816141

RESUMEN

BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. METHODS: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. FINDINGS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months). INTERPRETATION: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT. FUNDING: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.


Asunto(s)
Infecciones por VIH , Trasplante de Células Madre Hematopoyéticas , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Masculino , Estudios Prospectivos , Femenino , Adulto , Persona de Mediana Edad , VIH-1/inmunología , Trasplante Homólogo , Biomarcadores/sangre , Carga Viral , Anticuerpos Anti-VIH/sangre
5.
Heliyon ; 10(8): e29476, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38644847

RESUMEN

Over the last few years, the inclusion of psychosocial factors in the teaching and learning processes has become increasingly important due to their proven influence on students' academic performance, especially at the university stage. In this regard, the aim of this study is to analyse the impact of emotional intelligence and academic self-concept on the students' academic achievement. The results obtained revealed some differences according to gender in all the variables considered. Specifically, women presented higher levels of emotional attention, academic self-concept and performance, while men stood out in emotional clarity and emotional repair. The findings obtained show the importance of including psychosocial factors in university training plans.

6.
Nutrients ; 16(5)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38474734

RESUMEN

Bone represents a metabolically active tissue subject to continuous remodeling orchestrated by the dynamic interplay between osteoblasts and osteoclasts. These cellular processes are modulated by a complex interplay of biochemical and mechanical factors, which are instrumental in assessing bone remodeling. This comprehensive evaluation aids in detecting disorders arising from imbalances between bone formation and reabsorption. Osteoporosis, characterized by a reduction in bone mass and strength leading to heightened bone fragility and susceptibility to fractures, is one of the more prevalent chronic diseases. Some epidemiological studies, especially in patients with chronic kidney disease (CKD), have identified an association between osteoporosis and vascular calcification. Notably, low bone mineral density has been linked to an increased incidence of aortic calcification, with shared molecules, mechanisms, and pathways between the two processes. Certain molecules emerging from these shared pathways can serve as biomarkers for bone and mineral metabolism. Detecting and evaluating these alterations early is crucial, requiring the identification of biomarkers that are reliable for early intervention. While traditional biomarkers for bone remodeling and vascular calcification exist, they suffer from limitations such as low specificity, low sensitivity, and conflicting results across studies. In response, efforts are underway to explore new, more specific biomarkers that can detect alterations at earlier stages. The aim of this review is to comprehensively examine some of the emerging biomarkers in mineral metabolism and their correlation with bone mineral density, fracture risk, and vascular calcification as well as their potential use in clinical practice.


Asunto(s)
Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Fracturas Óseas , Osteoporosis , Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Osteoporosis/etiología , Densidad Ósea/fisiología , Insuficiencia Renal Crónica/complicaciones , Fracturas Óseas/etiología , Calcificación Vascular/complicaciones , Biomarcadores , Minerales
7.
Healthcare (Basel) ; 12(6)2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38540588

RESUMEN

Nowadays, obesity (OB) is one of the most important health problems in population-wide health. In addition to its physical consequences, it is a risk factor for the development of psychological problems, including body dissatisfaction (BD). This is why the treatment of BD is essential for its prevention. However, this has mostly been studied from a quantitative perspective, without focusing on the discomfort experienced by the person and the accompanying thoughts and emotions. In this study, 26 women with obesity (BMI > 30 kg/m2) participated, of whom 16 had high BD and 10 had low BD, as measured by the BSQ questionnaire. The women with high BD underwent six sessions of exposure to their own body in front of a mirror, recording the discomfort experienced with this vision during the session. In addition, all participants recorded positive and negative thoughts towards their body before and after these sessions. After the exposure treatment sessions, a reduction in symptomatology (BD, discomfort when visualizing one's own body) was observed, as well as a change in the thoughts expressed by the participants, both in quantity (fewer negative thoughts) and in quality (a more positive self-perception and/or in more respectful terms used towards themselves). In conclusion, such treatments prove to be effective in reducing subjective discomfort and body-related thoughts in women with obesity.

8.
Med Intensiva (Engl Ed) ; 48(5): 254-262, 2024 05.
Artículo en Inglés | MEDLINE | ID: mdl-38519374

RESUMEN

OBJECTIVE: To describe and characterize a cohort of octogenarian patients admitted to the ICU of the University Central Hospital of Asturias (HUCA). DESIGN: Retrospective, observational and descriptive study of 14 months' duration. SETTING: Cardiac and Medical intensive care units (ICU) of the HUCA (Oviedo). PARTICIPANTS: Patients over 80 years old who were admitted to the ICU for more than 24 h. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Age, sex, comorbidity, functional dependence, treatment, complications, evolution, mortality. RESULTS: The most frequent reasons for admission were cardiac surgery and pneumonia. The average admission stay was significantly longer in patients under 85 years of age (p = 0,037). 84,3% of the latter benefited from invasive mechanical ventilation compared to 46,2% of older patients (p = <0,001). Patients over 85 years of age presented greater fragility. Admission for cardiac surgery was associated with a lower risk of mortality (HR = 0,18; 95% CI (0,062-0,527; p = 0,002). CONCLUSIONS: The results have shown an association between the reason for admission to the ICU and the risk of mortality in octogenarian patients. Cardiac surgery was associated with a better prognosis compared to medical pathology, where pneumonia was associated with a higher risk of mortality. Furthermore, a significant positive association was observed between age and frailty.


Asunto(s)
Progresión de la Enfermedad , Unidades de Cuidados Intensivos , Humanos , Anciano de 80 o más Años , Estudios Retrospectivos , Masculino , Femenino , Unidades de Cuidados Intensivos/estadística & datos numéricos , Tiempo de Internación/estadística & datos numéricos , Respiración Artificial/estadística & datos numéricos , Procedimientos Quirúrgicos Cardíacos , Mortalidad Hospitalaria , Factores de Edad , Neumonía/epidemiología , Neumonía/mortalidad , Comorbilidad , España/epidemiología
9.
Int J Mol Sci ; 25(3)2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38339121

RESUMEN

Shortly after the discovery of Klotho, interest grew in its potential role in chronic kidney disease (CKD). There are three isoforms of the Klotho protein: αKlotho, ßKlotho and γKlotho. This review will focus on αKlotho due to its relevance as a biomarker in CKD. αKlotho is synthesized mainly in the kidneys, but it can be released into the bloodstream and urine as soluble Klotho (sKlotho), which undertakes systemic actions, independently or in combination with FGF23. It is usually accepted that sKlotho levels are reduced early in CKD and that lower levels of sKlotho might be associated with the main chronic kidney disease-mineral bone disorders (CKD-MBDs): cardiovascular and bone disease. However, as results are inconsistent, the applicability of sKlotho as a CKD-MBD biomarker is still a matter of controversy. Much of the inconsistency can be explained due to low sample numbers, the low quality of clinical studies, the lack of standardized assays to assess sKlotho and a lack of consensus on sample processing, especially in urine. In recent decades, because of our longer life expectancies, the prevalence of accelerated-ageing diseases, such as CKD, has increased. Exercise, social interaction and caloric restriction are considered key factors for healthy ageing. While exercise and social interaction seem to be related to higher serum sKlotho levels, it is not clear whether serum sKlotho might be influenced by caloric restriction. This review focuses on the possible role of sKlotho as a biomarker in CKD-MBD, highlighting the difference between solid knowledge and areas requiring further research, including the role of sKlotho in healthy ageing.


Asunto(s)
Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Envejecimiento Saludable , Proteínas Klotho , Humanos , Biomarcadores , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Factores de Crecimiento de Fibroblastos , Glucuronidasa , Envejecimiento Saludable/metabolismo , Minerales , Insuficiencia Renal Crónica/complicaciones , Proteínas Klotho/sangre , Proteínas Klotho/metabolismo
10.
Transplant Cell Ther ; 30(3): 306.e1-306.e12, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38184148

RESUMEN

Chimeric antigen receptor T cells (CAR-T) has emerged as a promising therapy, over 60% of patients fail to sustain a long-term response. The underlying factors that leads to the effectiveness of this therapy are not completely understood, CAR-T cell persistence and monitoring seems to be pivotal for ensuring a successful response. Various monitoring methods such as multiparametric flow cytometry (MFC) or quantitative PCR (qPCR) have been applied. Our objective is to develop digital PCR (dPCR) assays for detection and quantification of CAR-T cells, comparing them with MFC and qPCR. Samples taken at different follow-up times from 45 patients treated with CAR-T therapy were analyzed to assess the correlation between the different methodologies. dPCR presented a high correlation with MFC and qPCR (r = 0.97 and r = 0.87, respectively), while offering a higher sensitivity (0.01%) compared to MFC (0.1%) and qPCR (1%). dPCR emerged as an alternative and highly sensitivity method for monitoring CAR-T cell dynamics. This technique is well-suited for implementation in clinical practice as a complementary technique to MFC.


Asunto(s)
Linfoma de Células B , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Inmunoterapia Adoptiva/efectos adversos , Linfoma de Células B/etiología , Linfocitos T , Reacción en Cadena de la Polimerasa
11.
Transplant Cell Ther ; 30(2): 210.e1-210.e14, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38043802

RESUMEN

Post-transplantation cyclophosphamide (PTCy) has emerged as a promising approach for preventing graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is a lack of studies examining the impact of this GVHD prophylaxis when different donor types are used in patients with Hodgkin lymphoma (HL). This study compared the outcomes of patients with HL undergoing HSCT from HLA-matched donors, including matched sibling donors (MSDs) and matched unrelated donors (MUDs), and haploidentical donors, using PTCy as the GVHD prophylaxis approach in all cohorts. We retrospectively compared outcomes of allo-HSCT from 166 HLA-matched donors (96 sibling and 70 unrelated donors) and 694 haploidentical donors using PTCy-based GVHD prophylaxis in patients with HL registered in the European Society for Blood and Marrow Transplantation database from 2010 to 2020. Compared to HLA-matched HSCT, haploidentical donor HSCT was associated with a significantly lower rate of platelet engraftment (86% versus 94%; P < .001) and a higher rate of grade II-IV acute GVHD (34% versus 24%; P = .01). The 2-year cumulative incidence of nonrelapse mortality (NRM) was significantly lower in the HLA-matched cohort compared to the haploidentical cohort (10% versus 18%; P = .02), resulting in a higher overall survival (OS) rate (82% versus 70%; P = .002). There were no significant differences between the 2 cohorts in terms of relapse, progression-free survival, or GVHD-free relapse-free survival. In multivariable analysis, haploidentical HSCT was associated with an increased risk of grade II-IV acute GVHD and NRM and worse OS compared to HLA-matched HSCT. Our findings suggest that in the context of PTCy-based GVHD prophylaxis, transplantation from HLA-matched donors appears to be a more favorable option compared to haploidentical HSCT.


Asunto(s)
Enfermedad Injerto contra Huésped , Enfermedad de Hodgkin , Linfoma , Humanos , Enfermedad de Hodgkin/tratamiento farmacológico , Estudios Retrospectivos , Médula Ósea , Recurrencia Local de Neoplasia/complicaciones , Ciclofosfamida/uso terapéutico , Linfoma/complicaciones , Linfoma/tratamiento farmacológico , Enfermedad Injerto contra Huésped/prevención & control , Donante no Emparentado
13.
Sensors (Basel) ; 23(23)2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-38067975

RESUMEN

In this paper, the precise design of a high-power amplifier (HPA) is shown, along with the problems associated with the stability of "on-wafer" measurements. Here, techniques to predict possible oscillations are discussed to ensure the stability of a monolithic microwave-integrated circuit (MMIC). In addition, a deep reflection is made on the instabilities that occur when measuring both on wafer and using a mounted chip. Stability techniques are used as tools to characterize measurement results. Both a precise design and instabilities are shown through the design of a three-stage X-band HPA in gallium nitride (GaN) from the WIN Semiconductors Corp. foundry. As a result, satisfactory performance was obtained, achieving a maximum output power equal to 42 dBm and power-added efficiency of 32% at a 20 V drain bias. In addition to identifying critical points in the design or measurement of the HPA, this research shows that the stability of the amplifier can be verified through a simple analysis and that instabilities are often linked to errors in the measurement process or in the characterization of the measurement process.

14.
Blood Transfus ; 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-38063787

RESUMEN

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy is increasingly used in patients affected by B-cell lymphoma and acute lymphoblastic leukemia. For logistical reasons, initial apheresis products may be cryopreserved for shipment to manufacturing centers. Due to the characteristics of these patients, cells are often collected in large volumes, meaning more bags must be cryopreserved. This requires increased storage, time and monetary costs. In this context, we aimed to evaluate a high cell concentration cryopreservation protocol by centrifugation to standardize the initial CAR-T manufacturing procedure. MATERIALS AND METHODS: Sixty-eight processes of leukapheresis of 57 patients affected by refractory/relapsed B cell lymphoma and 9 patients affected by acute lymphoblastic leukemia who were eligible for anti-CD19 CAR-T cell treatment performed between June 2019 and October 2022 were analyzed. Whole blood count, percentage and number of T cells were assessed on the apheresis final product. The apheresis product, which was alternatively stored overnight at 4°C, was centrifuged, adjusting the volume to approximately 40 mL. The product was immediately cryopreserved to achieve a final cell concentration of 50-200×106 cells/ml for cryopreservation. RESULTS: Leukapheresis volume was reduced by almost fivefold (median: 185 to 40 mL), resulting in a higher product concentration in one bag. In addition, the number of non-target cells (monocytes, platelets and erythrocytes) was also reduced during the development of CAR T cell therapy, thereby maintaining T lymphocyte levels and providing a purer starting material. DISCUSSION: The advantages of the protocol include reducing economic costs, saving storage space, simplifying the manufacturing process, and facilitating shipping logistics. In conclusion, we present a validated, simple, and cost-effective cell enrichment processing protocol that provides high-quality cryopreserved products as starting material for the CAR-T cell manufacturing process.

15.
Genes (Basel) ; 14(10)2023 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-37895246

RESUMEN

Pseudomonas putida strain U can be grown using, as sole carbon sources, the biogenic amines putrescine or cadaverine, as well as their catabolic intermediates, ɣ-aminobutyrate or δ-aminovalerate, respectively. Several paralogs for the genes that encode some of the activities involved in the catabolism of these compounds, such as a putrescine-pyruvate aminotransferase (spuC1 and spuC2 genes) and a ɣ-aminobutyrate aminotransferase (gabT1 and gabT2 genes) have been identified in this bacterium. When the expression pattern of these genes is analyzed by qPCR, it is drastically conditioned by supplying the carbon sources. Thus, spuC1 is upregulated by putrescine, whereas spuC2 seems to be exclusively induced by cadaverine. However, gabT1 increases its expression in response to different polyamines or aminated catabolic derivatives from them (i.e., ɣ-aminobutyrate or δ-aminovalerate), although gabT2 does not change its expression level concerning no-amine unrelated carbon sources (citrate). These results reveal differences between the mechanisms proposed for polyamine catabolism in P. aeruginosa and Escherichia coli concerning P. putida strain U, as well as allow a deeper understanding of the enzymatic systems used by this last strain during polyamine metabolism.


Asunto(s)
Pseudomonas putida , Putrescina , Cadaverina/metabolismo , Putrescina/metabolismo , Putrescina/farmacología , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Poliaminas/metabolismo , Pseudomonas aeruginosa/genética , Escherichia coli/genética , Aminobutiratos/metabolismo , Carbono/metabolismo , Expresión Génica
16.
Artículo en Inglés | MEDLINE | ID: mdl-37660283

RESUMEN

BACKGROUND: Bone fragility fractures are associated with high morbidity and mortality. This study analysed the association between the current biochemical parameters of CKD-MBD and bone fragility fractures in the COSMOS project. METHODS: COSMOS is a 3-year, multicentre, open cohort, prospective, observational study carried out in 6797 hemodialysis patients (227 centres from 20 European countries). The association of bone fragility fractures (outcome) with serum calcium, phosphate and PTH (exposure), was assessed using Standard Cox proportional hazards regression and Cox proportional hazards regression for recurrent events. Additional analyses were performed considering all-cause mortality as a competitive event for bone fragility fracture occurrence. Multivariable models were used in all strategies, with the fully adjusted model including a total of 24 variables. RESULTS: During a median follow-up of 24 months 252 (4%) patients experienced at least one bone fragility fracture (incident bone fragility fracture rate 28.5 per 1000 patient-years). In the fractured and non-fractured patients, the percentage of men was 43.7% and 61.4%, mean age 68.1 and 63.8 years and a haemodialysis vintage of 55.9 and 38.3 months respectively. Baseline serum phosphate > 6.1 mg/dL (reference value 4.3-6.1 mg/dL) was significantly associated with a higher bone fragility fracture risk in both regression models (HR: 1.53[95%CI: 1.10-2.13] and HR: 1.44[95%CI: 1.02-2.05]. The significant association persisted after competitive risk analysis (subHR: 1.42[95%CI: 1.02-1.98]) but the finding was not confirmed when serum phosphate was considered as a continuous variable. Baseline serum calcium showed no association with bone fragility fracture risk in any regression model. Baseline serum PTH > 800 pg/mL was significantly associated with a higher bone fragility fracture risk in both regression models, but the association disappeared after a competitive risk analysis. CONCLUSIONS: Hyperphosphatemia was independently and consistently associated with an increased bone fracture risk, suggesting serum phosphate could be a novel risk factor for bone fractures in hemodialysis patients.

17.
Biomolecules ; 13(9)2023 09 20.
Artículo en Inglés | MEDLINE | ID: mdl-37759819

RESUMEN

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the H2O2-scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.


Asunto(s)
Insuficiencia Renal Crónica , Calcificación Vascular , Humanos , Animales , Ratas , Catalasa , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Peróxido de Hidrógeno , Oxidación-Reducción
18.
Arterioscler Thromb Vasc Biol ; 43(8): 1533-1548, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37381989

RESUMEN

BACKGROUND: Vascular calcification (VC) is a highly prevalent complication of chronic kidney disease (CKD) and is associated with the higher morbidity-mortality of patients with CKD. VDR (vitamin D receptor) has been proposed to play a role in the osteoblastic differentiation of vascular smooth muscle cells (VSMCs), but the involvement of vitamin D in VC associated to CKD is controversial. Our aim was to determine the role of local vitamin D signaling in VSMCs during CKD-induced VC. METHODS: We used epigastric arteries from CKD-affected patients and individuals with normal renal function, alongside an experimental model of CKD-induced VC in mice with conditional deletion of VDR in VSMC. In vitro, experiments in VSMC with or without VDR incubated in calcification media were also used. RESULTS: CKD-affected patients and mice with CKD showed an increase in VC, together with increased arterial expression of VDR compared with controls with normal renal function. Conditional gene silencing of VDR in VSMCs led to a significant decrease of VC in the mouse model of CKD, despite similar levels of renal impairment and serum calcium and phosphate levels. This was accompanied by lower arterial expression of OPN (osteopontin) and lamin A and higher expression of SOST (sclerostin). Furthermore, CKD-affected mice showed a reduction of miR-145a expression in calcified arteries, which was significantly recovered in animals with deletion of VDR in VSMC. In vitro, the absence of VDR prevented VC, inhibited the increase of OPN, and reestablished the expression of miR-145a. Forced expression of miR-145a in vitro in VDRwt VSMCs blunted VC and decreased OPN levels. CONCLUSIONS: Our study provides evidence proving that inhibition of local VDR signaling in VSMCs could prevent VC in CKD and indicates a possible role for miR-145a in this process.


Asunto(s)
MicroARNs , Insuficiencia Renal Crónica , Calcificación Vascular , Ratones , Animales , Músculo Liso Vascular/metabolismo , Receptores de Calcitriol/genética , Calcificación Vascular/genética , Calcificación Vascular/prevención & control , Riñón/metabolismo , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Vitamina D/metabolismo , Miocitos del Músculo Liso/metabolismo
19.
Front Psychol ; 14: 1124712, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37292507

RESUMEN

Higher education is a focus of increasing violent behavior. The evidence suggests an obsession to achieve the best academic performance in order to access working life. This research aims to develop an explanatory model of violent behavior and its relationship with self-concept and emotional intelligence according to in relation to their academic performance. A sample of 932 Spanish undergraduate students participated in the multi-group structural equation modeling. Findings revealed that students who have a higher academic performance have problems to control and regulate their emotions, showing signs of direct and indirect violence. Moreover, it was found that that emotional intelligence and self-concept have a direct influence on episodes of violent behavior, with academic performance being a key component affecting each variable. The present study provides some implications and suggests some avenues for future research.

20.
J Clin Med ; 12(9)2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37176531

RESUMEN

(1) Background: Facial scanners are used in different fields of dentistry to digitalize the soft tissues of the patient's face. The development of technology has allowed the patient to have a 3-dimensional virtual representation, facilitating facial integration in the diagnosis and treatment plan. However, the accuracy of the facial scanner and the obtaining of better results with respect to the manual or two-dimensional (2D) method are questionable. The objective of this clinical trial was to evaluate the usefulness and accuracy of the 3D method (a dual-structured light facial scanner) and compare it with the 2D method (photography) to obtain facial analysis in the maximum intercuspation position and smile position. (2) Methods: A total of 60 participants were included, and nine facial landmarks and five interlandmarks distances were determined by two independent calibrated operators for each participant. All measurements were made using three methods: the manual method (manual measurement), the 2D method (photography), and the 3D method (facial scanner). All clinical and lighting conditions, as well as the specific parameters of each method, were standardized and controlled. The facial interlandmark distances were made by using a digital caliper, a 2D software program (Adobe Photoshop, version 21.0.2), and a 3D software program (Meshlab, version 2020.12), respectively. The data were analyzed by SPSS statistical software. The Kolmogorov-Smirnov test revealed that trueness and precision values were normally distributed (p > 0.05), so a Student's t-test was employed. (3) Results: Statistically significant differences (p ≤ 0.01) were observed in all interlandmark measurements in the 2D group (photography) to compare with the manual group. The 2D method obtained a mean accuracy value of 2.09 (±3.38) and 2.494 (±3.67) in maximum intercuspation and smile, respectively. On the other hand, the 3D method (facial scanner) obtained a mean accuracy value of 0.61 (±1.65) and 0.28 (±2.03) in maximum intercuspation and smile, respectively. There were no statistically significant differences with the manual method. (4) Conclusions: The employed technique demonstrated that it influences the accuracy of facial records. The 3D method reported acceptable accuracy values, while the 2D method showed discrepancies over the clinically acceptable limits.

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